Exam Findings The Bloody Masquerader 6/11/2013 Jenny Z. Xu, O.D.
6/11/2013 Exam Findings The Bloody Masquerader Polypoidal Choroidal Vasculopathy Jenny Z. Xu, O.D. VA Palo Alto Health Care System Posterior Segment • VA – OD 20/200+ PHNI – OS 20/20 • Pupils – ERRL, no APD • Confrontations – EOM: full OU – VF: Full to finger counting OS, complete restriction OD temp, infra temp and superior temp • Anterior Segment: unremarkable OU, no rubeosis OU • TONOMETRY: 10/12 mmHg @ 1417 Polypoidal Choroidal Vasculopathy • Choroidal abnormality characterized by branching choroidal vascular network and vascular dilations of terminal choroidal vessels in shape of polyps • Also classified as a subtype of occult choroidal neovascularization • Initially described in 1982 by Yannuzzi “Idiopathic polypoidal choroidal vasculopathy”, also termed “posterior uveal bleeding syndrome” UC BERKELEY RESIDENT FORUM JUNE 2013 1 6/11/2013 PCV Epidemiology • African American females • More often in pigmented individuals such as Africans and Asians, but also found in Caucasians • Age of diagnosis from 20s to 80s, most common between the age of 60 and 70 years • 71% of PCV in Japanese population male and 75% of PCV in European population female • Predilection for macular and peripapillary locations • Bilateral in 14% Japanese population and 32% of Europeans diagnosed with PCV Diagnosis Clinical Presentation • Small to large branching of inner choroidal vessels with multiple polypoidal structures • Variable sized serosanguineous detachment of the RPE and neurosensory retina • Subretinal hemorrhages, lipid exudation • Subretinal fibrosis may result after resolution of serosanguineous complications • Pigment epithelial hyperplasia and degeneration ICGA and FA of PCV Gomi et al., Arch Clin Exp Ophthalmol, 2007 Early phase • ICGA is the gold standard for the diagnosis of PCV • FA not helpful due to obscuration of the choroid by the RPE • ICG allows for higher transmittance of light to choroid and better resolution of the vasculature • PCV definition by ICGA: single or multiple focal areas of hyperfluorescence arising from the choroid within the first 6 minutes after injection with or without associated vascular network. – Presence of orange‐red subretinal nodules with corresponding indocyanine green hyperfluoresence is pathognomonic of PCV UC BERKELEY RESIDENT FORUM JUNE 2013 Mid phase ICGA Mid to late phase Late phase FA 2 6/11/2013 OCT Pathophysiology Keane PA et al. Surv Ophthal, 2012 Double layer sign: hyper‐reflective layer beneath the RPE, inner boundary of Bruch’s membrane choriocapillaris complex Pathophysiology – Histology • Increased hyalinization of choroidal vessels and massive exudation of fibrin and blood plasma; degeneration of small vessels with thickened basement membrane • Hyalinization = extensive replacement of smooth muscle component by amorphous pseudocollagenous tissue of poorly defined nature, or arteriosclerotic changes that are found in the other parts of the body • Dilated venules and arterioles UC BERKELEY RESIDENT FORUM JUNE 2013 • Mechanism not well understood – agreement concerning the origination of the polyps from the inner choroid • Considered to be a subtype of exudative AMD (type 1, sub‐ RPE), or as a separate entity due to choroidal abnormalities • AMD and PCV share similar and differing genetic factors involving the complement system • According to Yannuzzi, PCV and AMD can be distinguished based on age, peripapillary locations of CNV, presence of soft drusen and ethnicity • Similarity of PCV to CSC Pathophysiology – Relationship to ARMD • Massive exudation of fibrin and blood plasma raises choroidal tissue pressure to produce protrusion of choroidal tissues through weakened RPE and Bruch’s • Choroidal neovascularization also found above the RPE in 2 out of 5 pathological specimens examined • Neovascularization may arise from RPE and Bruch’s membrane breaks • Overexpression of HTRA1 gene (responsible for extracellular matrix degradation) is associated with both macular degeneration and PCV – Overexpression decreases integrity of the Bruch’s membrane 3 6/11/2013 Pathophysiology – Relationship to CSC PCV the Masquerader • Choroidal vascular hyperpermeability: multifocal hyperfluorescence in mid and late phases of ICGA • Hyperpermeability in patients with PCV strongly associated with a history of CSC • Eyes with PCV and CSC had thicker choroid compared different types of ARMD • Increased thickness due to increased choriopapillary permeability possibly from increased hydrostatic pressure, leading also to RPE leaks and serous retinal detachments • CSC and PCV both related to choroid congestion and leakage rather than simply diseases of the Bruch’s membrane • Large subretinal hemorrhage and RPE atrophy may cause PCV to look like wet AMD • In patients diagnosed with AMD, 4.8% to 23% found to have PCV instead, more commonly diagnosed in Japanese individuals • Yannuzzi also reports PCV masquerading as CSC due to presence of serous pigment epithelial detachments and neurosensory retinal detachment – Re‐diagnosed with PCV based on ICGA findings that distinguished the PEDs from choroidal polyps Natural History • Highly variable • Remitting and relapsing course of chronic, multiple recurrent serosanguineous detachments • Approximately 50% of patients with posterior pole lesions have favorable visual outcome without treatment • Persistent bleeding involving the macula resulting in vision loss in others • Macular involvement ranges from 25 to 94% of patients • Visual prognosis depends on the location of and size of lesions UC BERKELEY RESIDENT FORUM JUNE 2013 Treatment: Combination Therapy • EVEREST study: multi‐centered, double masked, ICGA guided, randomized controlled trial involving 61 patients evaluating best treatment modality • Percent of polyp regression – Visudyne alone: 71.4%, VA improved by 7.5 letters – 3 x 0.5 mg monthly Lucentis alone: 28.6%, VA improved by 9.2 letters – Visudyne + Lucentis: 77.8%, VA improved by 10.9 letters, lowest rate of PDT – related hemorrhages • Recommend either combination therapy or ICGA guided PDT • Anti‐VEGF: effective for reabsorption of subretinal fluid; monotherapy recommended if PDT contraindicated 4 6/11/2013 Management Algorithm References • • • • • • • • • • • • • • • • • • Koh et al, 2013 • • • Yannuzzi LA. Idiopathic polypoidal choroidal vasculopathy. Macula Society Meeting, 1982, Miami, FL. Yannuzzi LA, Freund KB, Goldbaum M et al. Polypoidal choroidal vasculopathy masquerading as central serous chorioretinopathy. Ophthalmology 2000;107(4):767‐77. Lafaut BA, Leys AM, Snyers B, et al. Polypoidal choroidal vasculopathy in Caucasians. Graefes Arch Clin Exp Ophthalmol 2000;238:752–759. Koh A, Lee WK, Chen LJ, et al. EVEREST study: efficacy and safety of verteporfin PDT in combination with ranibizumab or alone versus ranibizumab monotherapy in patients with symptomatic macular polypoidal choroidal vasculopathy. Retina 2012;32:1453–1464. Ahuja RM, Stanga PE, Vingerling JR, et al. Polypoidal choroidal vasculopathy in exudative and haemorrhagic pigment epithelial detachments. Br J Ophthalmol 2000;84:479–484. Gomi F, Sawa M, Mitarai K, et al. Angiographic lesion of polypoidal choroidal vasculopathy on indocyanine green and fluorescein angiography. Graefes Arch Clin Exp Ophthalmol 2007;245:1421–1427. Koh A, Chen LJ, Chen SJ, et al. Polypoidal choroidal vasculopathy: evidence‐based guidelines for clinical diagnosis and Treatment. Retina, J Retinal and Vitreous Diseases 2013;33(4):686‐716 Imamura Y, Engelgert M, Iida T et al. Polypoidal choroidal vasculopathy: A Review. Surv Ophthalmol 2010; 55(6):501‐515 Koizumi H, Yamagashi T, Yamazai T et al. Relationship between clinical characteristics of polypoidal choroidal vasculopathy and choroidal vascular hyperpermeability. Am J Ophthalmol 2012:1‐9 Hayashi K, Hasegawa Y and Tokoro T. Indocyanine green angiograophy of central serous chorioretinopathy. Int Ophthalmol 1986; 9(1):37‐41 Hochman MA, Seery CM and Zarbin MA. Pathophysiology and management of subretinal hemorrhage. Surv Ophthalmol 1997; 42(3):195‐213 Birkholz ES, Johnson AT and Russell SR. Retinal Artery Macroaneurysm. EyeRounds.org. Posted July 7, 2010; Available from: www.EyeRounds.org/cases/113‐RAMA.htm Kim SW, Oh J, Kwon SS et al. Comparision of choroidal thickness among patients with healthy eyes, early age‐related maculopathy, neovasculra age‐ related macular degeneration, central serous chorioretinopathy, and polypoidal choroidal vasculopathy. Retina J Retina and Vitreous Disease 2011; 31(9): 1904‐1911 Sato T, Kishi S, Watanabe G et al. Tomographic features of branching vascular networks in polypoidal choroidal vasculopathy. Retina, J of Retina and Vitreous Diseases 2007; 27(5)589‐594 Miki A, Honda S, Kojima H et al. Visual outcome of photodynamic theraphy for typical neovascular age‐related macular degeneration and polypoidal choroidal vasculopathy over 5 years of follow up. Jpn J Ophthalmol 2013; 57:301‐307 Giovannini A, Amato GP. D‘Altobrando E, Giuliani M. Optical coherence tomography (OCT) in idiopathic polypoidal choroidal vasculopathy (IPCV). Doc Ophthalmol.1999;97(3‐‐4):367—71 Silva R. Neovascular Phenotypes: polypoidal choroidal vasculopathy. AMDBook. Last revision Oct 2011; available from: http://amdbook.org/content/neovascular‐phenotypes‐polypoidal‐choroidal‐vasculopathy Keane PA, Patel PJ, Liakopoulos S et al. Evaluation of Ag‐related macular degeneration with Optical Coherence Tomography. Surv Ophthalmol 2012; 57(5)389‐414 Koizumi H, Yamagishi T,, Yamazaki T et al. Subfoveal choroidal thickness in typical age‐related macular degeneration and polypoidal choroidal vasculopathy. Graefes Arch Clin Exp Ophthalmol 2011, 249:1123‐1128 Sato T, Kishi S, Watanabe G et al. Tomograhic features of branching vascular networks in polypoidal choroidal vasculopathy. Retina 2007, 27:587‐594 Glaucoma Progressive Optic Neuropathy Normal Tension Glaucoma The Problem with Low Pressure Kristin Symon, OD UC Berkeley School of Optometry Ocular Disease Resident June 23, 2013 UC BERKELEY RESIDENT FORUM JUNE 2013 • Degeneration of retinal ganglion cells and axons • Loss of rim tissue • Glaucomatous cupping • Corresponding visual field defects that follow RNFL loss 5 6/11/2013 2nd Leading Cause of Vision Loss Worldwide • Over 40 million people worldwide (12.3%) • Open angle glaucoma affects more than 2 million individuals in the US • By 2020 there will be at least 3 million affected • 50% of individuals go undiagnosed Normal tension glaucoma • Open angle glaucoma with untreated IOP within the normal range (22 mmHg) • 20‐39% of patients with OAG in the US and Europe • Up to 30% of patients are under age 50 • The Collaborative Normal Tension Glaucoma Study (CNTGS) showed that a 30% decrease in IOP resulted in preservation of visual function (Quigley, 2004) (MacDonald, 2012) Examination Findings Patient DY 26 yo Korean Female Examination Findings OD OS BCVA Refraction 20/20‐ ‐5.75 ‐0.50 x 015 20/20‐ ‐4.25 ‐1.50 x 155 Anterior Segment Unremarkable Unremarkable IOP (@16:36) 18 mmHg 19 mmHg Gonioscopy Cilliary body 360 Cilliary body 360 Pachymetry 580 microns 573 microns Presented to clinic on 9/24/2010 CC: decreased peripheral vision Previous diagnosis of Glaucoma ‐ diagnosed in Korea 8/2010 Current treatment: Betoptic 1 gtt OU BID Pre‐treatment IOP: OD 19 mmHg, OS 20 mmHg UC BERKELEY RESIDENT FORUM JUNE 2013 6 6/11/2013 Optic Nerve and Retinal Nerve Fiber Layer Analysis ✕ Hereditary optic neuropathy Normal MRI Ruled out by history ✕ ✕glaucomatous Non‐ Mass lesion of orbit or cranium Trauma cupping and visual field defects ✕ Heavy metal ✕ Humphrey Visual Field 30‐2 Threshold Normal Tension Glaucoma • Visual field defects respecting horizontal • Nasal step and arcuate defects • Splinter hemorrhage at optic disc Intracranial Mass ✕ Infection Auto‐ immune • Neuroretinal rim pallor exceeds cupping • Vertical alligned visual field defects • Younger age • Reduced visual acuity Lab Workup Normal (Greenfield et al, 1998) UC BERKELEY RESIDENT FORUM JUNE 2013 7 6/11/2013 Disc Hemorrhage • Some studies report increased frequency of disc hemorrhages in normal tension glaucoma • Controversial support of a vascular etiology for NTG • Jonas suggests that disc hemorrhages are found in most patients with glaucoma, however, they are more apparent in NTG due in part to different pressure mechanics at the optic nerve head • The CNTGS reported that a history of migraine HA and presence of Disc hemorrhage were both related with progression of glaucoma Treatment • Patient DY was started on Xalatan 1 gtt OU QHS • Latanoprost (generic for Xalatan) is more effective at reducing IOP during sleeping hours than Timolol (Liu et al, 2003) Progression of Normal Tension Glaucoma CNTGS 20% 80% 20% of patients with Normal Tension Glaucoma showed progression despite a 30% reduction in IOP • Progression – Visual field defect – Neuroretinal rim thinning – Nerve fiber layer defects • Adjunctive topical therapy added: Ocular Perfusion Low ocular vascular perfusion is a risk factor for glaucoma • No tool to directly measure blood flow at the optic nerve head • Extrapolate expected perfusion through a combination of systemic blood pressure and IOP Mean ocular perfusion pressure: MOPP = 2/3 [DBP + 1/3(SBP – DBP)] – IOP Diastolic ocular perfusion pressure: DOPP = DBP – IOP – Alphagan 1gtt OU BID DOPP less than 55 mmHg = twice the relative risk of glaucoma DBP = diastolic BP SBP = systolic BP UC BERKELEY RESIDENT FORUM JUNE 2013 (Quaranta et al, 2013) 8 6/11/2013 Diastolic Ocular Perfusion Pressure for DY 60 55 50 DOPP OD 45 40 DOPP OS Cut off 55 • Upward trend in DOPP with treatment • However DOPP remains less than 55 mmHg 35 Neuroprotection The search for pressure independent treatment for glaucoma • Aim to prevent or delay the death of neurons Possible Neuroprotective Agents ‐ antioxidants ‐ alpha‐2‐agonists ‐ N‐methyl‐D‐aspartate (NMDA) receptor antagonists ‐ glutamate inhibitors ‐ calcium channel blockers ‐ polyamine antagonists ‐ nitric oxide synthetase inhibitors ‐ Ginkgo biloba ‐ melatonin ‐ vitamin B‐12 UC BERKELEY RESIDENT FORUM JUNE 2013 Cerebrospinal Fluid Pressure Examining the dark side • Trans‐laminar pressure differential is determined by the IOP and the orbital CSF‐pressure • Trans‐laminar pressure is likely more important in glaucoma development than the transcorneal pressure measured by applanation • Low CSF‐pressure increases the risk for glaucoma (normal CSF‐P is 5 to 15 mmHg) References AGIS Investigators. The advanced glaucoma intervention study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration. Am J Ophthalmology 139, no. 4 (2000): 429‐440. Bengtsson B, Leske MC, Yang Z, Heijl A, EMGT Group. Disc hemorrhages and treatment in the early manifest glaucoma trial. Ophthalmology 115, no. 11 (2008): 2044‐2048. Chang EE, Goldberg JL. Glaucoma 2.0: Neuroprotection, neuroregeneration, neuroenhancement. Ophthalmology 119 (2012): 979‐986. Choi J, Jeong J, Cho H, Kook MS. Effect of nocturnal blood pressure reduction on circadian fluctuation of mean ocular perfusion pressure: a risk factor for normal tension glaucoma. Investigative Ophthalmology & Visual Science 47, no. 3 (2006): 831‐836. Coleman AL, Miglior S. Risk factors for glaucoma onset and progression. Survey of Ophthalmology 53 (2008): S3‐S10. Collaborative Normal‐Tension Glaucoma Study Group. The effectiveness of intraocular prssure reduction in the treatment of normal‐tension glaucoma. Am J Ophthalmology 126, no. 4 (1998): 498‐505. Ernest, PJ, Schouten JS, Beckers HJ, Hendrikse F, Prins MH, Webers CA. An evidence‐based review of prognostic factors for glaucomatous visual field progression. Ophthalmology 120 (2013): 512‐519. Greenfield DS, Siatkowski RM, Glaser JS, Schatz NJ, Parrish RK. The cupped disc: who needs neuroimaging? Ophthalmology 105, no. 10 (1998): 1866‐1874. Jonas JB, Wang N. Association between arterial blood pressure, cerebrospinal fluid pressure and intraocular pressure in the pathophysiology of optic nerve head diseases. Clinical & Experimental Ophthalmology 40 (2012): e233‐e234. Krupin T, Liebman JM, Greenfield DS, Ritch R, Gardiner S. A randomized trial of brimonidine versus timolol in preserving visual function: results from the Low‐ pressure Glaucoma Treatment Study. Am J Ophthalmology 151, no. 4 (2010): 671‐681. Liu CJ, Ko YC, Cheng CY, Chiu AW, Chou JC, Hsu WM, Liu JH. Changes in intraocular pressure and ocular perfusion pressure after latanoprost 0.005% or brimonidine tartrate 0.2% in normal‐tension glaucoma patients. Ophthalmology 109 (2012): 2241‐2247. Liu JHK, Medeiros FA, Slight JR, Weinreb RN. Comparing diurnal and nocturnal effects of brinzolamide and timolol on intraocular pressure in patients receiving Latanoprost monotherapy. Ophthalmology 116 (2009): 449‐454. Liu JHK, Zhang X, Kripke DF, Weinreb RN. Twenty‐four‐hour intraocular pressure pattern associated with early glaucomatous changes. Invest Ophthalmol Vis Sci. 44 (2003): 1586‐90. Macdonald, D. Under pressure: a review of normal‐tension glaucoma. Canadian Journal of Optometry 74, no. 4 (2012): 33‐44. Medeiros FA, Lisboa R, Weinreb RN, Liebmann JM, Girkin C, Zangwill LM. Retinal ganglion cell count estimats associated with early development of visual field defects in glaucoma. Ophthalmology in press (2012): 1‐9. Morgan WH, Yu DY, Balaratnasingam C. The role of cerebrospinal fluid pressure in glaucoma pathophysiology: the dark side of the optic disc. J Glaucoma 17, no. 5 (2008): 408‐413. Quaranta L, Katsanos A, Russo A, Riva I. 24‐hour intraocular pressure and ocular perfusion pressure in glaucoma. Survey of Ophthalmology 58, no. 1 (2013): 26‐ 41. Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmology 90 (2006): 262‐267. Ramli N, Nurull BS, Hairi NN, Mimiwati Z. Low nocturnal ocular perfusion pressure as a risk factor for normal tension glaucoma. Preventative Medicine in press (2012): 1‐3. Ren R, Jonas JB, Tian G, Zhen Y, Ma K, Li S, Wang H, Li B, Zhang X, Wang N. Cerebrospinal fluid pressure in glaucoma. Ophthalmology 117, no. 2 (2010): 259‐266. Shields, MB. Normal‐tension glaucoma: is it different from primary open‐angle glaucoma? Current Opinion in Ophthalmology 19 (2008): 85‐88. Sung, K.R., S. Lee, S.B. Park, J. Choi, S.T. Kim, S.C. Yun, S.Y. Kang, J.W. Cho, M.S. Kook. Twenty‐four hour ocular perfusion pressure fluctuation and risk of normal‐ tension glaucoma. Integrative Ophthalmology & Visual Science 50, no. 11 (November 2009): 5266‐5274. 9 6/11/2013 D.G. Case Report • 61 year old white male – Relates sudden blurred vision OD for 1 month NVG Stephen Chang, O.D. Optometry Resident Sierra Nevada HCS Reno VA June 23rd, 2013 • Glaucoma suspect OU, pseudophake OU • History of poor compliance with follow up visits • Uncontrolled type 2 diabetes, hypertension, hyperlipidemia – Family history of diabetes in father & grandfather D.G. Clinical Data • His vision was CF @ 3 ft OD, 20/25 OS with moderate myopic and astigmatic Rx • 2+ RAPD OD, with inferior VF constriction detected on confrontation fields • IOPs were 42/20 • NVI superior/temporally OD • Scattered NVA in the superior/temporal quadrant. • Hypotensive agents (brimonidine, cosopt) decreased the IOP to 25 OD within 2 hrs. UC BERKELEY RESIDENT FORUM JUNE 2013 10 6/11/2013 3 Days Later • Assessment: – NVG secondary to CRVO OD • Plan: – Same day Ophthalmology consult/IFVA – Pt started on maximum hypotensive gtts – hypercoaguable state, CBC, Lipid profile, & Carotid U/S ordered Neovascular Glaucoma • Late presentation of serious underlying systemic and ocular pathology • Arises in response to profound retinal ischemia* • Poor prognosis, highly resistant to treatment • PRP performed OD • IOP 32/16 • Due to AC cells/flare, pred forte added to gtt regimen • Scheduled for next available anti‐VEGF injection OD NVG Definitions • Wills Eye Manual – Stage 1: NVI/NVA – Stage 2: NVI/NVA + increased IOP – Stage 3: 1, 2 + partial/complete angle closure • Moraczewski et. al – IOP > 21 mmHg associated with NVI/NVA • Ehlers et. al – IOP ≥ 4mmHg higher in eye with NV – NVI/NVA with concurrent use of hypotensive gtts UC BERKELEY RESIDENT FORUM JUNE 2013 11 6/11/2013 Signs/Symptoms • • • • • • • • • • • Asymptomatic Decreased vision Pain/photophobia Redness Neovascularization of the anterior chamber Elevated intraocular pressure Anterior chamber cells/flare Corneal edema Ectropion uveae Synechial angle closure Cupping of the optic nerve Treatment • • • • • • • • • • Prevention Reduction of the IOP Panretinal Photocoagulation Pars plana vitrectomy (PPV) Endolaser (EL) photocoagulation Anti‐VEGF agents* Trabeculectomy Glaucoma Drainage Implants (GDI) Cyclophotocoagulation (CPC) Cryoretinopexy UC BERKELEY RESIDENT FORUM JUNE 2013 Differential Diagnosis • Acute angle‐closure glaucoma • Inflammatory open‐angle glaucoma • Ocular ischemic syndrome Pan‐Retinal Photocoagulation2 • Gold standard for initial treatment of anterior segment neovascularization due to retinal hypoxia • Reduction of ischemic drive through fragmentation of blood column in all new vessels • Noninvasive with few complications • Effects are long‐lasting but often take weeks to occur • Application of burns to cover a major portion of the retina in all quadrants • 1200‐1600 burns of 500 micron spot size applied* 12 6/11/2013 The role of Antiangiogenic Agents • Regression of neovascularization occurs quickly but is temporary and recurrence is possible* • Small studies (Iliev, Gheith) have shown that early treatment with intravitreal bevacizumab (IVB) improved NVG outcomes Outcomes of Treatment of Neovascular Glaucoma with Intravitreal Bevacizumab. Moraczewski et. al. Br. J Ophthalmol 2009; 93:589‐593. • Bascom Palmer Eye Institute Standard of Care – 1. IVB at time of diagnosis – 2. PRP shortly thereafter • Or Endolaser/PPV (if cloudy media) – 3. Medical/surgical intervention (if necessary) – If IVB is administered before formation of PAS, IOP may be controlled without surgical procedures9 Proposed Treatment Algorithm for Neovascular Glaucoma8 Follow up Schedule • Every 2‐3 weeks1 (Hayreh, prospective study) • Every 3‐4 weeks for the first 6 mos, less frequently thereafter.1 (Hayreh, clinically) • NVI/NVA may occur quickly (days to weeks).10 • Rate at which PAS develops is remarkably variable (days to weeks).4 UC BERKELEY RESIDENT FORUM JUNE 2013 13 6/11/2013 Ocular Neovascularization Associated with Central and Hemicentral Retinal Vein Occlusion. Hayreh et al. Retina 32:1553‐1565, 2012. Cumulative Probability of development of NV from onset of ischemic CRVO1 References 1. 2. 3. 4. 5. 6. 7. Iris Angle Glaucoma within 1 month 16% 8% 4% within 2 months 26% 15% 11% within 3 months 33% 28% 20% within 6 months 49% 37% 29% 14. within 9 months 52% 39% 34% 15. within 5 years 63% 49% 39% Posner‐Schlossman Syndrome and Inflammatory Glaucoma 8. 9. 10. 11. 12. 13. 16. 17. Ocular neovascularization associated with central and hemicentral retinal vein occlusion. Hayreh et al. Retina 32:1553‐1565, 2012. Ophthalmic surgery: Principle & Practice. Spaeth, George. 1990. W.B. Saunders company. Novartis Pharmaceuticals Australia Pty Limited. http://www.avastin‐hcp.com/bevacizumab/moa/proposed‐mechanism‐of‐action Glaucoma, Chandler and Grant. 4th edition. Epstein et. al. 1997. Chapter 225: Neovascular Glaucoma; Ophthalmology. 04/05/11; Fanous, Maher. Erythropoietin levels in aqueous humor of patients with glaucoma. Nassiri et. al. Molecular Vision 2012; 18:1991‐1995. Intraocular Pressure Abnormalities Associated with Central and Hemicentral Retinal Vein Occlusion. Hayreh et. al. Ophthalmology 2004; 111; 133‐141 Medical and Surgical Treatment of Neovascular Glaucoma. Olmos, Lee. International Ophthalmology Clinics. Vol 51, No 3, 27‐36. Outcomes of Treatment of Neovascular Glaucoma with Intravitreal Bevacizumab. Moraczewski et. al. Br. J Ophthalmol 2009; 93:589‐593. Combination Intravitreal Bevacizumab/panretinal Photocoagulation vs Panretinal Photocoagulation Alone in the Treatment of Neovascular Glaucoma. Ehlers et. al. Retina 28:696‐702, 2008. Surgical Outcome of Intravitreal Bevacizumab and Filtration Surgery in Neovascular Glaucoma. Kitnarong et. al. Adv. Ther. 2008;25(5):438‐443. Panretinal Photocoagulation with Simultaneous Cryoretinopexy or Intravitreal Bevacizumab for Neovascular Glaucoma. Tatsumi et al. Graefes Arch Clin Exp Ophthalmol. 2012. Mermoud A, Salmon JF, Alexander P, et al. Molteno tube implantation for neovascular glaucoma. Long‐term results and factors influencing the outcome. Ophthalmology. 1993;100:897–902. Krupin T, Kaufman P, Mandell AI, et al. Long‐term results of valve implants in filtering surgery for eyes with neovascular glaucoma. Am J Ophthalmol. 1983;95: 775–82. Anti‐VEGF Therapy for the treatment of glaucoma: a focus on ranibizumab and bevacizumab. Park et. al. Expert Opin Biol Ther. 2012 Dec; 12(12):1641‐7. Surgical results of Ahmed Valve Implantation with Intraoperative Bevacizumab Injection in Patients with Neovascular Glaucoma. Kyoung et. al. J Glaucoma 2012;21:331‐336. Combined Intravitreal Bevacizumab and Trabeculectomy with Mitomycin C vs Trabeculectomy with Mitomycin C Alone for Neovascular Glaucoma. Takihara et. al. J Glaucoma 2011;20:196‐201. 65 year old male • CC: “pressure” in eye – Constant pressure and discomfort within OS since this morning with foggy vision, mild dull headache, and light sensitivity • Medical History: – Hypertension and hyperlipidemia medically‐controlled Tran Nguyen VA Palo Alto HCS Primary Care Optometry and Low Vision Rehabilitation UC BERKELEY RESIDENT FORUM JUNE 2013 • Negative family medical history • Family ocular history: father blind due to glaucoma 14 6/11/2013 History Continued: • Patient Ocular History: – “Inflammatory glaucoma vs Posner‐Schlossman Syndrome OS” – Resolved BRVO OS 2009 without complications – Meibomian gland dysfunction – Mild cataracts OU – History of trauma, punched in OD when young Intraocular Pressures: 02/26/13: •20/65 @1438 Brimonidine, cosopt, latanoprost, prednisolone acetate 1% •20/61 @1550 Brimonidine, cosopt, latanoprost, prednisolone acetate 1% •20/60 @1611 Brimonidine, cosopt, latanoprost, prednisolone acetate 1% •18/49 @1650 • ‐‐/55 @1850 Diamox 500mg po • ‐‐/55 @2250 Anterior chamber paracentesis OS: •‐‐/13 @2332 Diamox 250mg q6h, Vigamox qid, cosopt tid, brimonidine tid, prednislone acetate 1% qid • Ocular Medications: – Cosopt bid OS with good compliance • Last dose: twice this morning at 9:00am Differential Diagnosis • Acute angle closure • Neovascular glaucoma • Hypertensive uveitic syndromes – – – – • • • • • Posner‐Schlossman Syndrome Herpetic keratouveitis Fuch’s heterochromic iridocyclitis Cytomegalovirus iridocyclitis Inflammatory/uveitic glaucoma Primary open angle glaucoma Non‐arteritic ishemic optic neuropathy Optic neuritis Masquerade syndromes UC BERKELEY RESIDENT FORUM JUNE 2013 Posner‐Schlossman Syndrome: Recurrent, unilateral anterior uveitis with increased IOP Minimal conjunctival injection Corneal edema Few nonpigmented keratic precipitates, few cells and mild flare reaction • Angles open • Pupils: iris heterochromia and anisocoria • Trabeculitis • • • • – Exact mechanism unknown 15 6/11/2013 Pathogenesis of PSS: • Spectrum of inflammatory responses to members of herpesviridae family – Cytomegalovirus • Local antibodies – Herpes simplex virus “Inflammatory Glaucoma?" • Persistent or recurrent IOP elevation anatomical and physiological damage to ONH • Higher suspicion for uveitic etiology with unilateral glaucomatous optic neuropathy • Axonal and secondary retinal ganglion cell loss Optic rim excavation & RNFL thinning • Vascular/Autonomic imbalance • HLA‐Bw54 positive Elevated IOP and Non‐glaucomatous Optic Neuropathy • Optic atrophy & PSS • NAION & PSS Management: • Nonsurgical treatment – Corticosteroids – Topical nonsteroidal antiinflammatories – Aqueous suppressants • Flow = perfusion pressure resistance to flow • Perfusion pressure = • Surgical intervention with medical failure or high risk cases – Filtering surgery Mean blood pressure – IOP • Trabeculectomy with antimetabolites • Glaucoma drainage implants • Disc pallor in 20‐39% with acute angle closure • Reduced S‐cone component of ERG in PSS • Diagnostic labs and imaging when warranted Kim et al 2012. Korean J Ophthalmol UC BERKELEY RESIDENT FORUM JUNE 2013 16 6/11/2013 Intraocular Pressures: 02/26/13: •20/65 @1438 Brimonidine, cosopt, latanoprost, prednisolone acetate •20/61 @1550 Brimonidine, cosopt, latanoprost, prednisolone acetate •20/60 @1611 Brimonidine, cosopt, latanoprost, prednisolone acetate •18/49 @1650 • ‐‐/55 @1850 Diamox 500mg po • ‐‐/55 @2250 Anterior chamber paracentesis OS: • ‐‐/13 @2332 Diamox 250mg q6h, Vigamox qid, Dorz‐Tim tid, Alphagan tid, PF qid 02/27/13 13/40 @1230 02/28/13: ‐‐/13 @0711 POD#1 s/p Ahmed OS 03/04/13: ‐‐/14 @1505 POD#5 Atropine qd OS, PF qid OS, Vigamox qis OS 03/18/13: 20/21 @1500 PF qid OS 04/04/13: 19/18 @1328 PF qid OS, Timolol 0.25% bid OS 05/14/13: 18/18 @1013 Timolol 0.25% bid OS 05/28/13 Follow‐Up: •VA: 20/25 OU •1+ left APD •IOP: 18/23 mmHg at 0815 C/D: 0.35H/V C/D: 0.7H/0.75V UC BERKELEY RESIDENT FORUM JUNE 2013 17 6/11/2013 Summary: Posing as Posner’s? HVF OS 2006 vs 2013: • Previously thought to be “self‐limiting” and “benign” – 26.4% develop glaucomatous damage – Jap et al • CMV and HSV leading infectious etiologies for PSS – Still poorly understood • Distinct clinical entities of HSV uveitic glaucoma and CMV iridocyclitis • Multifactorial and complicated spectrum of conditions • Prophylactic treatment in consideration of NAION associated with acute cyclitis episodes • Important to monitor for glaucomatous and non‐ glaucomatous optic neuropathy 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. References Beck RW, Servais GE, Hayreh SS. Anterior ischemic optic neuropathy. IX. Cup‐to‐disc ratio and its role in pathogenesis. Ophthalmology. 1987 Nov;94(11):1503‐8. Bloch‐Michel E, Dussaix E, Cerqueti P, Patarin D. Possible role of cytomegalovirus infection in the etiology of the Posner‐Schlossmann syndrome. Int Ophthalmol. 1987 Dec;11(2):95‐6. Bodh SA, Kumar V, Raina UK, Ghosh B, Thakar M. 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Ophthalmology. 2007 Dec;114(12):2338‐44. Epub 2007 Aug 27. Darchuk V, Sampaolesi J, Mato L, Nicoli C, Sampaolesi R. Optic nerve head behavior in Posner‐Schlossman syndrome. Int Ophthalmol. 2001;23(4‐6):373‐ 9. Da Mata A, Burk SE, Netland PA, Baltatzis S, Christen W, Foster CS. Management of uveitic glaucoma with Ahmed glaucoma valve implantation. Ophthalmology. 1999 Nov;106(11):2168‐72. Dinakaran S, Kayarkar V. Trabeculectomy in the management of Posner‐Schlossman syndrome. Ophthalmic Surg Lasers. 2002 Jul‐Aug;33(4):321‐2. Falcon MG, Williams HP. Herpes simplex kerato‐uveitis and glaucoma. Trans Ophthalmol Soc U K. 1978 Apr;98(1):101‐4. Goldberg DE, Freeman WR. Uveitic angle closure glaucoma in a patient with inactive cytomegalovirus retinitis and immune recovery uveitis. Ophthalmic Surg Lasers. 2002 Sep‐Oct;33(5):421‐5. Green RJ. Posner‐Schlossman syndrome (glaucomatocyclitic crisis). Clin Exp Optom. 2007 Jan;90(1):53‐6. Harrington JR. Posner‐Schlossman syndrome: a case report. 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Iwao K, Inatani M, Seto T, Takihara Y, Ogata‐Iwao M, Okinami S, Tanihara H.Long‐term Outcomes and Prognostic Factors for Trabeculectomy With Mitomycin C in Eyes With Uveitic Glaucoma: A Retrospective Cohort Study. J Glaucoma. 2012 Aug 14. Jap A, Sivakumar M, Chee SP. Is Posner Schlossman syndrome benign? Ophthalmology. 2001 May;108(5):913‐8. Jones R 3rd, Pasquale LR, Pavan‐Langston D.Herpes simplex virus: an important etiology for secondary glaucoma. Int Ophthalmol Clin. 2007 Spring;47(2):99‐107 UC BERKELEY RESIDENT FORUM JUNE 2013 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. Kass MA, Becker B, Kolker AE. Glaucomatocyclitic crisis and primary open‐angle glaucoma. Am J Ophthalmol. 1973 Apr;75(4):668‐73. Kim R, Van Stavern G, Juzych M. Nonarteritic anterior ischemic optic neuropathy associated with acute glaucoma secondary to Posner‐Schlossman syndrome. Arch Ophthalmol. 2003 Jan;121(1):127‐8. Kim TH, Kim JL, Kee C.Optic disc atrophy in patient with Posner‐Schlossman syndrome. Korean J Ophthalmol. 2012 Dec;26(6):473‐7. Epub 2012 Nov 12. Knox DL. Clinical features of cytomegalovirus anterior uveitis in immunocompetent patients. Am J Ophthalmol. 2008 Oct;146(4):625; author reply 625‐6. Li J, Ang M, Cheung CM, Vania M, Chan AS, Waduthantri S, Yang H, Chee SP. Aqueous cytokine changes associated with Posner‐Schlossman syndrome with and without human cytomegalovirus 2012;7(9):e44453. Epub 2012 Sep 13. Maeda H, Nakamura M, Negi A. Selective reduction of the S‐cone component of the electroretinogram in Posner‐Schlossman syndrome. Eye (Lond). 2001 Apr;15(Pt 2):163‐7. Mietz H, Aisenbrey S, Ulrich Bartz‐Schmidt K, Bamborschke S, Krieglstein GK.Ganciclovir for the treatment of anterior uveitis. Graefes Arch Clin Exp Ophthalmol. 2000 Nov;238(11):905‐9. Mohamed Q, Zamir E.Update on Fuchs' uveitis syndrome. Curr Opin Ophthalmol. 2005 Dec;16(6):356‐63. Moorthy RS, Mermoud A, Baerveldt G, Minckler DS, Lee PP, Rao NA. Glaucoma associated with uveitis. Surv Ophthalmol. 1997 Mar‐Apr;41(5):361‐94. Ozdal PC, Vianna RN, Deschênes J. Ahmed valve implantation in glaucoma secondary to chronic uveitis. Eye (Lond). 2006 Feb;20(2):178‐83. Papadaki TG, Zacharopoulos IP, Pasquale LR, Christen WB, Netland PA, Foster CS.Long‐term results of Ahmed glaucoma valve implantation for uveitic glaucoma. Am J Ophthalmol. 2007 Jul;144(1):62‐69. Epub 2007 May 9. Posner A., Schlossman A, Syndrome of unilateral recurrent attacks of glaucoma with cyclitis symptoms. Arch Ophthalmol, 39 (1948), pp. 517–535 Roth M, Simmons RJ. Glaucoma associated with precipitates on the trabecular meshwork. Ophthalmology. 1979 Sep;86(9):1613‐9. Sangha SS. Posner Schlossman syndrome. Ophthalmology. 2002 Mar;109(3):409. Shazly TA, Aljajeh M, Latina MA.Posner‐Schlossman glaucomatocyclitic crisis. Semin Ophthalmol. 2011 Jul‐Sep;26(4‐5):282‐4. Sng CC, See JS, Ngo CS, Singh M, Chan YH, Aquino MC, Tan AM, Shabana N, Chew PT. Changes in retinal nerve fibre layer, optic nerve head morphology, and visual field after acute primary angle closure. Eye (Lond). 2011 May;25(5):619‐25. Epub 2011 Mar 25. Suh MH, Kim SH, Park KH, Kim SJ, Kim TW, Hwang SS, Kim DM. Comparison of the correlations between optic disc rim area and retinal nerve fiber layer thickness in glaucoma and nonarteritic anterior ischemic optic neuropathy. Am J Ophthalmol. 2011 Feb;151(2):277‐86.e1. Epub 2010 Dec 18. Sood GC, Kapoor S, Krishnamurthy MS, Reddy S, Sook M. Posner‐Schlossman syndrome surgical management. Eye Ear Nose Throat Mon, 55 (1976), pp. 29–32 Takahashi T, Ohtani S, Miyata K, Miyata N, Shirato S, Mochizuki M. A clinical evaluation of uveitis‐associated secondary glaucoma. Jpn J Ophthalmol. 2002 Sep‐Oct;46(5):556‐62. Takusagawa HL, Liu Y, Wiggs JL.Infectious theories of Posner‐Schlossman syndrome. Int Ophthalmol Clin. 2011 Fall;51(4):105‐15. 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Epub 2011 Jan 19. 18 6/11/2013 Case Report • 30 year old Caucasian female Lights Out By Baljit Sohal, OD Central California VA Health Care Systems, Fresno CA Case report continued • VA – c/o vision loss in the right eye for past three days – started with some blurriness and felt the “lights went out” in that eye • Medical and ocular history: unremarkable Case continued… • Slit lamp findings – NLP OD, 20/25 OS sc • Entrance testing – Pupils: PERRL 2+APD OD – Extraocular motility testing: • FROM OU with mild pain on down gaze OD – Confrontational visual field testing – Conjunctiva: Temporal pinguecula OU – Cornea: clear OU – Anterior chamber: deep/quiet OU – Lens: 1+ Nuclear sclerotic cataracts OU – IOP: 15mmHg OD, 18mmHg OS by Goldmann • Unable to test OD, full OS UC BERKELEY RESIDENT FORUM JUNE 2013 19 6/11/2013 Case continued… • 60D undilated fundoscopic view – 0.35V/0.40H OD, 0.50V/0.55H OS – Pink and healthy nerves OU – Macula flat (-)exudates/heme/srf OU – Vessels were normal OU Imaging continued… • MRI of the orbits/brain – Asymmetric enlargement, edema, and enhancement of the right optic nerve anterior to the chiasm involving the intraorbital segment – Brain parenchyma intact, without characteristic white matter lesions of multiple sclerosis UC BERKELEY RESIDENT FORUM JUNE 2013 What to do? • Assessment – Retrobulbar optic neuritis OD • Plan – CT scan of brain and orbits followed by MRI of brain and orbits with gadolinium – RTC 7-14 days for recheck Optic neuritis and clinical features • Acute demyelinating disease of the optic nerve • Isolated neurological finding or can be associated with MS • Monocular vision loss – 10% in both eyes • simultaneous • rapid succession • Eye pain on eye movements • Visual field defect – central scotoma 20 6/11/2013 Clinical features continued… • Anterior optic neuritis • Retrobulbar optic neuritis – Papillitis • hyperemia • swelling of the disc – Blurry disc margins – Distended veins – APD – Color vision – Normal fundoscopic examination – Disc pallor after few weeks – APD – Color vision – Most common Optic Neuritis Treatment Trial • Results – Patients receiving IV methylprednisolone followed by oral prednisone recovered vision faster than placebo • Final visual outcome was only slightly better at 6 mo – Oral prednisone alone provided no benefit in rate of recovery or final outcome at six months Optic neuritis treatment • Optic Neuritis Treatment Trial – Corticosteroids in the treatment of acute optic neuritis – 457 patients with acute optic neuritis • Oral prednisone x 14 days(1mg per kg of body weight per day) • Intravenous methylprednisolone (1g/day for 3 days) followed by oral prednisone for 11 days • Oral placebo MRI and MS • Typical brain lesion plaques that are seen in patients with MS – Ovoid – Periventricular – white matter lesions – Larger than 3mm • ONTT follow up showed the risk of MS after Optic neuritis • higher rate of new attacks UC BERKELEY RESIDENT FORUM JUNE 2013 21 6/11/2013 Optic Neuritis Treatment Trial • Cumulative probability of developing MS by 15 year examination was 50% – Strongly related to presence of lesions on the baseline brain MRI – No difference among treatment groups • Risk of developing MS was highest in the first five years overall • In patients w/o lesions, risk was higher for women(16%), or with retrobulbar ON What is MS • Autoimmune • Demyelinating disorder of the nervous system – Commonly manifested with visual involvment • Chronic relapsing and remitting, episodic disease UC BERKELEY RESIDENT FORUM JUNE 2013 ONTT and MS continued • No baseline MRI lesions – Approx 15% developed MS during 5 years – 25% developed MS during 15 year follow-up • One or more lesions – Approx 42% developed MS during 5 years – 72% developed MS during 15 year follow-up • Low risk of MS – no MRI/brain lesions, – male gender – optic disc edema and atypical optic neuritis Multiple sclerosis symptoms • Numbness or weakness in one or more limbs • Double vision or blurring of vision • Tingling or pain in parts of your body • Electric-shock sensations that occur with certain head movements • Tremor, lack of coordination or unsteady gait • Slurred speech • Fatigue • Dizziness 22 6/11/2013 More ocular involvement • Isolated cranial nerve palsies – Mostly CN 6 • Internuclear Ophthalmoplegia • Defects with Saccades and Pursuits • Nystagmus – INO, vestibular, pendular, gaze-evoked • Retinal periphlebitis (10-39%) – Perivascular exudation, hemorrhage, and retinal venous sheathing “Worst Headache of my life" Treatment and Management of Pituitary Macroadenoma References • • • • • • • • Mathews, Michaela. Nonarteritic anterior ischemic optic neuropathy. Current Opinion in Ophthalmology. Lippincott Williams & Wilkins. 2005 Beck, Roy, M.D, et al. A Randomized, Controlled Trial of Corticosteroids in the Treatment of Acute Optic Neuritis. The New England Journal of Medicine. Massachusetts medical society. 1992 Myelitis Association. The Transverse Myelitis Association, Optic Neuritis. TMA. 2012 Osborne, Benjamin, et al. Optic Neuritis: Pathophysiology, Clinical Feautures, and Diagnosis. Wolters Kluwer Health. Uptodate. 2013 Gal, Robin, et al. Visual Function More Than 10 Years After Optic Neuritis: Experience of the Optic Neuritis Treatment Trial. American Journal of Opthalmology. Elsevier Inc, 2004 Gal, Robin, et al. Multiple Sclerosis Risk after Optic Neuritis: Final Optic Neuritis Treatment Trial Follow up. Arch Neurol. 2008 June; 65(6):727-732 Volpe, Nicholas, et al. Optic Neuritis and risk of MS: Differential diagnosis and management. Cleveland clinic Journal of Medicine. March 2009 vol 76 3 181-190 Chen, Ling, et al. Ocular Manifestations of Multiple Sclerosis. Current Opinion in Ophthalmology 2005. 16:315 -320 D.M 64 yo WM presented to outside Emergency Department “Worse headache of my life” Tresca Truong Optometry Resident VA Sierra Nevada Health Care SystemReno 6/23/13 UC BERKELEY RESIDENT FORUM JUNE 2013 HPI Crushing, alleviated by nothing Nausea Vomiting Woke him from sleep No altered mental status, fever or weight loss No vision loss Systemic medical history Chronic pain Colon polyps Bipolar Disorder Anxiety Medications: Oxycodone HCL, Morphine Social history Lives alone (-) smoking (+) alcohol: “few times a week” 23 6/11/2013 Differential Diagnosis • • • • • • • Pituitary Gland Migraine Tension headache Cluster headache CVA Intracerebral hemorrhage Intracranial mass Sinusitis Reno VA Right superior visual field loss, losing 11 lbs in one month, confusion, difficulty with memory’ Patient Medical History Anxiety Psychosocial disorder Mood disorder Low back pain Gout Medication seeking behavior Hypercholesteremia Hypogonadism Medications Allopurinol, calcium, docusate, morphine, oxycodine, respiridone, simvastatin, tamulosin Social History Smoking: quit 40 years ago EtOH: 3-4x a week, sometimes 6 pack of beer/day, with wine at night Illicit Drugs: history of cocaine and marijuana use UC BERKELEY RESIDENT FORUM JUNE 2013 24 6/11/2013 10mm Treatment 1,2,3 • Monitor if <10mm • Endoscopic Transphenoidal Tumor Resection • Radiotherapy only if residual tumor tissue left over after surgery • Labs must be ordered to determine if secreting or non-secreting. – – – – – – – – TSH Thyroxine GH Prolactin Estrogen/Testosterone ACTH LH ADH UC BERKELEY RESIDENT FORUM JUNE 2013 Pituitary Adenoma • Common benign tumors 1,2,3 • 10-12% of adult intracranial neoplasms 2,5,8 • Categorization 6,7,8 – Size (micro vs macro) • Stage 1 <10mm • Stage 2 >10mm • Stage 3 locally invasive • Stage 4 diffusely invasive – Secretions (nonfunctioning vs functioning) • Incidence rates 8,9 – Higher in women in early life – More common with men later in life – Higher in African American and lowest in American Indians/Alaskan Natives 25 6/11/2013 Stage of Improvement 11 Visual Disturbance 1,3,7,10 • Stage One (surgery to one week) – Visual Field Defects 96% • Unilateral 32.9% • Bilateral 67.1% • Rapid recovery, result of recovery of nerve conduction by removal of physiologic conduction block – Visual Acuity 63% – Color vision 38.7-56% – Optic Atrophy 28-49% – Ptosis 6% – Diplopia 10% – Nerve palsy 2% • Stage Two (1 month to 4 months) – Delayed recovery is thought to be the result of remyelination of decompressed optic pathways • Stage Three Positive • • • • • Young age Short duration of symptoms Good acuity Small field loss Normal color vision – Late recovery over months to years. Not well studied Negative • Optic disc pallor • High MD absolute value • Long duration of symptoms • Large Tumor size UC BERKELEY RESIDENT FORUM JUNE 2013 Complete Recovery Partial Recovery Unchanged Visual Field (95%) 48.9% 46.8% 4.3% Visual Acuity 33.35% 33.35% 33.3% Color Vision 30% 52.8% (-) Optic Disc Pallor 16.9% 50% (-) 26 6/11/2013 11/19/2012 Follow-up Follow-up • Biopsy:Non-functioning • Pt reported intermittent left lower VF defect • Given size of mass, will likely need radiation • VA: 20/60 PH 20/30 OD 20/40 PH 20/30-1 OS • Start on testosterone • (-)APD • Ishihara: 14/14 OU • Confrontational fields: left lower quadrant VF constriction • EOMs revealed full ductions and versions Anterior Segment • Unremarkable Posterior Segment • C/Ds: 0.20h/v OU • Macula: normal • Vessels: normal caliber • Periphery: (-)holes and detachments References What can we do? 1. 1. 2. 3. 4. 5. Filters to enhance contrast Low vision exam for devices that may help with magnification Prisms or mirrors to compensate for field loss or diplopia Vision therapy Visual fields important to see if they meet state law requirements for driver’s license. UC BERKELEY RESIDENT FORUM JUNE 2013 Barzaghi et al. Prognostic Factors of Visual Field Improvement after Trans-sphenoidal Approach for Pituitary Macroadenomas: Review of the Literature and Analysis by Quantitative Method. NeuroSurgery Review. 2012. 35:369-379 2. Dhasmana et al. Visual Fields at Presentation and After Trans-Sphenoidal Resection of Pituitary Adenomas. J. Ophthalmic Vis Res. 2011. 6(3):187-191. 3. Schmalisch et al. Predictors for Visual Dysfunction in Nonfunctioning Pituitary Adenomas-Implications for Neurosurgical Management. Clinical Endocrinology. 2012. 77:728-734. 4. Pituitary Macroadenoma Endonasal Endoscopic Removal. St. John’s Health Center. 5. Lee et al. The Volume of Tumor Mass and Visual Field Defect in Patients with Pituitary Macroadenoma. Korean J. Ophthalmology. 2011. 25(1): 37-41. 6. Daly et al. The Epidemiology and Management of Pituitary Incidentalomas. Hrm. Rs. 2007 68(5): 195-198 7. De Aguiar Ribeiro Cury et al. Non-functioning Pituitary Adenomas: Clinical Feature, Laboratorial an Imaging Assessment, Therapeutic Management and Outcome. Arq Bras Endocrinol Metab. 2009. 53 (1): 31-39. 8. Caputo et al. Gender Differences in Presentation and Outcome of Nonfunctioning Pituitary Macroadenomas. Clinical Endocrinology. 2013. 78:564-570. 9. McDowell et al. Demographic Differences in Incidence for Pituitary Adenoma. Pituitary. 2011. 14(10):23-30. 10. Poon et al. Patterns of Visual Loss Associated with Pituitary Macroadenomas. Aus and NZ Journal of Ophth. 1995. 23(2):107-115. 11. Kerrison et al. Stages of Improvement in Visual Fields After Pituitary Tumor Resection. Am. Journal of Ophth. 2000. 130 (6): 813-820. 27 6/11/2013 Differential Diagnosis of an Esotropia with an Abduction Deficit in Infants Jill Kronberg, OD June 23, 2013 3‐Year‐Old Male Incidence of Strabismus • 3‐5% of children affected by strabismus • Esotropia appears 3‐5 X more than exotropia in children • 50% of childhood esotropia has an accommodative component • After age 4 the prevalence of exotropia exceeds esotropia • Intermittent exotropia is the most common type of exotropia Exam Findings • Abduction deficit • Second Opinion • • Intolerant of spectacle wear Current Rx: • OD: ‐1.25 DS • OS: ‐2.00 DS • Personal Medical History • • • • Born past‐term Mild asthma NICU for breathing difficulty No medications Refractive Findings Visual Acuity • Cardiff @ 100 cm • OD: 0.6/1.9 M ~20/63 • OS: 0.6/1.2 M ~20/40 • OU: 20/50 Retinoscopy • OD: plano ‐1.25 x 090 • OS: plano – 1.50 x 090 UC BERKELEY RESIDENT FORUM JUNE 2013 – OD: ‐2 restriction – OS: ‐4 restriction • Compensatory head posture • Ocular posture: appeared aligned in primary gaze • Contrast sensitivity: 1.6% Michelson Contrast • Normal color vision • Anterior Segment: Unremarkable • Posterior Segment: Unremarkable Differential Diagnosis • Sixth Cranial Nerve Palsy • Type I Duane Syndrome • Infantile Esotropia • Accommodative Esotropia • Mobius Syndrome 28 6/11/2013 Sixth Cranial Nerve Palsy • Sudden onset inward eye‐turn • Limited aBduction • Head‐turn towards affected side – Eliminates diplopia Etiology • Most common cause: Intracranial tumor • Post‐vaccination • Post‐febrile infection • Hydrocephalus • Trauma Intracranial tumors • Worst prognosis in symptoms – Large restriction of abduction – Most likely to be bilateral • Associated neurologic symptoms – Headache, ataxia, and other cranial nerve palsies – Onset within one week of strabismus • Types of tumors – Brainstem glioma – Cholesterol granuloma of petrous bone – Eosinophilic granuloma of petrous bone http://www.meddean.luc.edu/lumen/MedEd/grossanatomy/h_ n/cn/cn1/images/cn‐6.jpg http://avserver.lib.uthsc.edu:8080/Medicine/eye_exam/SixthNervePalsy.jpg Prognosis Type I Duane Syndrome • Mechanism is unknown • Full recovery expected in benign palsy • Spontaneously resolves within 6 months Treatment • • • • Thorough case history Associated neurologic symptoms: MRI/refer Spontaneous resolution No resolution post 6 months – Botulinum toxin – Surgery – better outcome closer to onset • Congenital disorder affecting ocular motility • Characterized by: – Limited aBduction – Narrowing of the intrapalpebral fissure on adduction – Retraction of the globe on adduction http://www.mrcophth.com/ocularmotility/duaneb.JPG UC BERKELEY RESIDENT FORUM JUNE 2013 29 6/11/2013 • • • • Characteristics Type I Duane Syndrome is most common classification of Duane syndrome Female > male Possible strabismus in primary position OS more frequently affected in a unilateral presentation Etiology • Absence of abducens nucleus • Anomalous innervation by CN III to the lateral rectus muscle – MR & LR contract simultaneously causing globe retraction • No associated degeneration associated absence of nucleus Prognosis/Treatment • Prognosis: – Non‐progressive • Treatment – Strabismus surgery if strabismus in primary gaze – Best outcome with bilateral esotropia Duane syndrome Prognosis/Treatment Infantile Esotropia • Previously known as congenital esotropia – Not initially present in neonates • Presents before 6 months of age • Large angle esotropia – (>40 prism diopters) • Vertical misalignment – Dissociated vertical deviation (DVD) – Over‐action of the inferior oblique • Abduction obtainable http://health‐ 7.com/Atlas%20of%20Pediatric%20Physical%20Diagnosis/Esodeviations/ 1 Accommodative Esotropia • Over‐convergence associated with accommodative system • Three origins of accommodative esotropia • Prognosis – Amblyopia treatment • Good visual acuity outcomes • Unlikely to appreciate stereopsis • Treatment – Treat amblyopia – Surgery • Contraindicated before four months of age • Degree of esotropia may resolve before six months of age • Correct refractive error before surgery UC BERKELEY RESIDENT FORUM JUNE 2013 – Hypermetropia – High ratio of accommodative convergence to accommodation (AC/A) – Combination of hypermetropia and AC/A ratio Types of Accommodative Esotropia • Partially accommodative – Residual esotropia with full (+) Rx – Hypothesized: secondary anatomical contracture of medial rectus • Fully accommodative – Corrected with full (+) Rx 30 6/11/2013 Prognosis/Treatment Mobius Syndrome •Unilateral or Bilateral CN VI Palsy •Impairment of aBduction • Prognosis: Excellent – Potential for stereopsis – Normal visual acuity • Treatment – Treatable with glasses / bifocals • Ensure add bisects the pupil!! – Surgery contraindicated •CN VII Palsy •Non‐progressive Characteristic Appearance • • • • Mask‐like facies Drooling Lagophthalmos Associated limb anomalies – Club foot, fused digits, absence of portion of limb – Poland’s anomaly • Syndactyly + malformation of unilateral pectoralis muscle http://bjo.bmj.com/content/86/8/923.full http://www.mastersinhealthcare.net/blog/2010/10‐diseases‐you‐didnt‐know‐existed/ Etiology • Unknown • Hypothesis – Transitory interruption of fetal blood supply to brain stem • Secondary to tetratogen exposure during the first trimester • Tetratogen: gestational hyperthermia, electric shock, abuse of benzodiazepines, alcohol, etc. Prognosis/Treatment Differential Summary • • • • • Mobius Rare, allow head movement VI Cranial Nerve Palsy Refer OMD/Consider MRI Infantile Esotropia Co‐management (Provide Rx) Accommodative Esotropia Full (+), don’t refer Duane Syndrome Relax, it’s stable! • Prognosis: Good – Stable condition • Treatment – Allow patient to move head into restricted fields UC BERKELEY RESIDENT FORUM JUNE 2013 31 6/11/2013 The rest of the story… • Remaining patient history – Mild left facial nerve palsy – No limb anomalies • Previously diagnosed with Mobius syndrome at 8 months of age References • • • Assessment • Mobius syndrome – Previously diagnosed • Regular astigmatism • • • • • • • Plan • Discontinue spherical myopic spectacle wear • Allow pt to move his head • Inform pediatrician/physical therapists to allow head movement • Seek care yearly • • • • • • • • • • Batra, Noopur N., CO. "Comparison of Primary Position Measurements and Abduction Deficit Between Type I Duane Syndrome and Sixth Cranial Nerve Palsy." Journal of Neuro‐Ophthalmology 31 (2011): 117‐20. Print. Birch, E., D. Stager, K. Wright, R. Beck, and Pediatriceyediseaseinvestigator. "The Natural History of Infantile Esotropia during the First Six Months of Life1, 2." Journal of American Association for Pediatric Ophthalmology and Strabismus 2.6 (1998): 325‐28. Print. Birth, Eileen E. "Stereoacuity Outcomes Following Treatment of Infantile and Accommodative Esotropia." Optometry & Vision Science 86.6 (2009): 647‐ 52. Print. Briegel, W. "Neuropsychiatric Findings of Mobius Sequence ‐ a Review." Clinical Genetics 70.2 (2006): 91‐97. Print. Carta, Arturo, MD. "Ophthalmologic and Systemic Features in Mobius Syndrome: An Italian Case Series." Ophthalmology 118.8 (2011): 1518‐523. Print. Cheng, Daryl R. "Recurrent 6th Nerve Palsy in a Child following Different Live Attenuated Vaccines: Case Report." BMC Infectious Diseases 12.105 (2012): 1‐5. Print. Dotan, Gad. "The Role of Neuroimaging in the Evaluation Process of Children with Isolated Sixth Nerve Palsy." Child's Nervous System 29 (2013): 89‐92. Print. Hutchinson, Amy. "Refractive Surgery for Accommodative Esotropia: Past, Present, and Future." European Journal of Ophthalmology 22.6 (2012): 871‐ 77. Print. Ing MR. “Long‐term follow‐up of congenital esotropia in a population based study.” Journal of the American Association for Pediatric Opthalmology and Strabismus 2009: 427 Johansson, Maria, MD. "Autistic Spectrum Disorders in Mobius Sequence: A Comprehensive Study of 25 Individuals." Developmental Medicine & Child Neurology 43 (2001): 338‐45. Print. Kang, N., and J. Demer. "Comparison of Orbital Magnetic Resonance Imaging in Duane Syndrome and Abducens Palsy." American Journal of Ophthalmology 142.5 (2006): 827‐34.e2. Print. Khan, A., and D. Oystreck. "Clinical Characteristics of Bilateral Duane Syndrome." 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Ophthalmology 118.3 (2011): 581‐85. Print. Olitsky, Scott E., and Leonard B. Nelson. "Strabismus Disorders." Pediatric Clinical Ophthalmology: A Color Handbook. London: Manson, 2012. 51‐57. Print. Pollard, Zane F., MD. "Accommodative Esotropia During the First Year of Life." Archives of Ophthalmology 94 (1976): 1912‐913. Print. Sachdeva, Virender, MS. "Surgical Management of Bilateral Esotropic Duane Syndrome." Journal of American Academy of Pediatrics Ophthalmology and Strabismus 16.5 (2012): 445‐48. Print. Terzis, Julia K., and Katerina Anesti. "Developmental Facial Paralysis: A Review." Journal of Plastic, Reconstructive & Aesthetic Surgery 64.10 (2011): 1318‐333. Print. Case Report: AC • 91 y.o. Hispanic male • CC: Severe eye pain and sudden vision loss OS Ocular Ischemic Syndrome Lavender Orr, O.D. VACCHCS Optometry Resident June 23,2013 UC BERKELEY RESIDENT FORUM JUNE 2013 – Began two days ago without relief – Seen by outside general ophthalmologist • Elevated IOP 60‐70mmHg OS • Avastin intraocular injection • Prescribed topical anti‐hypertensives & oral Diamox • Pertinent medical Hx – – – – – Congestive heart failure COPD Transient ischemic attack Hypertension Obesity 32 6/11/2013 Exam Findings • Normal Findings OD • BCVA: – OS: HM • Pupils: – OS: mydriatic pupil • Confrontations: – OS: Constricted 360 • Biomicroscopy OS – 2‐3+ diffuse microcystic edema – Formed AC – Definite 360 iris rubeosis • Tonometry: – 16/59mmHg @11:11am – Oral acetazolamide administered w/topical antihypertensives & Muro 128 ung – ‐‐/52mmHg @ 12:23pm – Additional dose of aforementioned therapy A&P • Plan: • Assessment: – Neovascular glaucoma OS • Acute ocular hypertensive crisis – Most likely etiologies • OIS • CRAO • old CRVO • Fundus view: – Attenuated arteries OS – No dilated/tortuous veins – No obvious intraretinal hemorrhaging Neovascular glaucoma • What is NVG? – Chronic, progressive ocular ischemia – Radical IOP increase – Severe vision loss • Common causes: – DM – CRVO – OIS UC BERKELEY RESIDENT FORUM JUNE 2013 – Acetazolamide 250mg PO QID – Anti hypertensives w/atropine BID – Order carotid ultrasound – Lab testing: ESR, CRP, CBC, Chem 7 – RTC 1 week CRAO • Source: – Retinal emboli • Symptoms: – Sudden, painless loss of vision • Signs: – (+) APD – Attenuated arteries – Cherry red spot in acute phase – Emboli 33 6/11/2013 Ischemic CRVO • Source: Ocular ischemic syndrome • Source – Thrombus formation – Carotid artery occlusion • Symptoms: • Symptoms – Sudden, painless loss of vision – Eye pain & decreased acuity • Signs • Signs – (+) APD – Widespread hemorrhaging – Dilated/tortuous retinal veins – Mid peripheral intraretinal hemorrhages – Dilated retinal veins without tortuosity In office follow up #1 • Good compliance, no pain • Lab Testing: – Normal, mildly elevated ESR • Tonometry: – ‐‐/40mmHg • Carotid Ultrasound • Same day PRP w/ retinal specialist • Vascular consultation – – – – Benefits of CEA MRA 325 mg aspirin daily Statin medication – Greater than 70% stenosis to near occlusion bilaterally UC BERKELEY RESIDENT FORUM JUNE 2013 Ocular ischemic syndrome • Rare & severe form of ocular ischemia – 7.5/1,000,000 • Common symptoms – Ocular pain – Amaurosis fugax – TIA symptoms 34 6/11/2013 Demographics & Etiology • Commonly seen in • Hemodynamically patients over the age of significant ipsilateral 65 internal carotid artery occlusion • Men 2x more than – Rare: occlusion of women ophthalmic artery or • Other chronic illnesses occlusion along aortic • 5 year mortality rate of arch 40% – Greater than 90% Diagnosis & Treatment • Ophthalmodynamometry – Decreased central retinal artery perfusion • Fluorescein angiography – Delayed & patchy choroidal filling • Carotid ultrasound – Benefit of MRA – High grade stenosis of 70‐ 99% – 92/1,415 = 6.5% – 2.0% ‐ disabling stroke or death – Gold standard treatment – Successful for preventing progression of chronic ocular ischemia – Risky! – Obstruction <99% • Early diagnosis is critical! Crest: CEA vs CAS NASCET • The North American Symptomatic Carotid Endarterectomy Trial • Carotid Endarterectomy (CEA) • The Carotid Resvascularization Endarterectomy vs Stenting Trial • Overall, no significant difference at four years – >70 years: CEA – <70 years: CAS – Stroke • 2.3% vs 4.1% – Myocardial infarction • 2.3 vs 1.1% – Death • 0.3% vs 0.7% UC BERKELEY RESIDENT FORUM JUNE 2013 35 6/11/2013 BEWARE!! • Increased risk of CRAO • Immediate and rapid changes often affects ocular structures – Relative hypotony – Rapid increase in IOP – Pain!! Fighting ischemia • Best to manage with: • PRP – Anti‐hypertensives that decrease aqueous production – Topical cycloplegic – Constant solution • Anti VegF – Temporary solution – Good in cases of media opacity • PRP + anti VegF – Increased success rate for glaucoma surgery References Clinical pearls • • Early & prompt diagnosis is key to prevent fatal effects • Work closely with PCP & other specialists • Patient education • • • • • • • • • • • • • • • • • • UC BERKELEY RESIDENT FORUM JUNE 2013 Back, Martin et al. Magnetic resonance angiography is an accurate imaging adjunct to duplex ultrasound scan in patient selection for carotid endarterectomy. Journal of Vascular Surgery 2000;32(3):429‐440. Barnett, H.J.M. et al. North American Symptomatic Carotid Endarterectomy Trial (NASCET). Stroke: A Journal of Cerebral Circulation 1998;29(6)1270. Brown, Gary C et al. The ocular ischemic syndrome. Current Opinion in Ophthalmology 1994;5(3):14‐20. Ciftci, Suleyman et al. Intravitreal bevacizumab combined with panretinal photocoagulation in the treatment of open angle neovascular glaucoma. European Journal of Ophthalmology 2009;19(6)1028‐1033. Eid, TE, et al. Tube shunt surgery versusneodymium: YAG photocoagulation in the mangement of neovascular glaucoma. Opthalmology 1997;104(10):1692‐1700. Ferguson, Gary G et al. The North American Symptomatic Carotid Endarterectomy Trial: Surgical Results in 1415 Patients. Stroke: A Journal of Cerebral Circulation 1999;30(9)1751‐1758. Gross, Ronald. Neovascular glaucoma and ocular ischemic syndrome. Journal of Glaucoma 2000; 9:409‐412. Haymore, Jonathan G et al. Retinal vascular occlusion syndromes. International Ophthalmology Clinics 2009;49(3):63‐79. Hazin, Ribhi et al. Ocular ischemic syndrome: recent trends in medical management. Current Opinion in Ophthalmology 2009;20:430‐433. Kawaguchi, Shoichiro et al. Effect of carotid endarterectomy on chronic ocular ischemic syndrome due to internal carotid artery stenosis. Neurosurgery 2001;48(2) 328‐333. London, Nikolas et al. Update and review of central retinal vein occlusion. Current Opinion in Ophthalmology 2011;22:159‐165. Malhotra, Raman et al. Management of ocular ischaemic syndrome. British Journal of Ophthalmology 2000;84:1428‐1431. Mantese, Vito A. MD, et al. The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST). Stroke 2010;41:S31‐34. Olmos, Lisa C et al. Medical and surgical treatment of neovascular glaucoma. Int Ophthalmology Clin 2011;51(3):27‐36. Raghavan, Prashant et al. Magnetic resonance angiography of the extracranial carotid system. Topics in Magnetic Resonance Imaging 2008;19(5):241‐ 249. Saito, Yoshiaki et al. Beneficial effects of preoperative intravitreal bevacizumab on trabeculectomy outcomes in neovascular glaucoma. Acta Ophthalmologica 2010;88(1):96‐102. Wakabayashi, Taku et al. Intravitreal bevacizumab to treat iris neovascularization and neovascular glaucoma secondary to ischemic retinal diseases in 41 consecutive cases. Ophthalmology 2008;115:1571‐1580. Winterkorn, Jacqueline M.S. et al. Recovery from ocular ischemic syndrome after treatment with verapamil. Journal of Neuro‐Ophthalmology 1995;15(4):209‐211. Wolintz, Robyn J. Carotid endarterectomy for ophthalmic manifestations: Is it ever indicated? Journal of Neuro‐Ophthalmology 2005;25(4):299‐302. Olmos, Lisa C MD, et al. Medical and Surgical Treatment of Neovascular glaucoma. Internation Ophthalmology Clinics 2011;51(3):27‐36. 36 6/11/2013 INTRODUCTION • VITREOUS HEMORRHAGE Incidence: 7 cases per 100,000 • Presenting symptoms: floaters, cloudy vision, shadows, cobwebs • Diagnosis: observation • Complete examination: DEVELOPMENT, DIFFERENTIAL DIAGNOSIS, AND MANAGEMENT RECOMMENDATIONS • anterior vitreous at the slit lamp • Indirect ophthalmoscopy with depression scleral • B-scan Marta Banh O.D. • DFE of the contralateral eye San Francisco VAMC Resident • IOP* June 23, 2013 • Gonioscopy* • Management: dictated by underlying etiology POSTERIOR VITREOUS DETACHMENT IN HEALTHY ADULTS LIQUEFACTION OF HUMAN VITREOUS Volume of Gel and Liquid Vitreous Vitreous Syneresis and PVD Posterior Vitreous Detachment (PVD) is the process by which cortical vitreous gel splits away from the internal limiting membrane (ILM) of the retina. • Epidemiology • 53% in those older than age 50 • 65% in those over age 65 • 72-100% in aphakic eyes • May occur up to 10 years early in myopic patients • Higher incidence in women than men Volume of gel vitreous remains stable until about age 40, then it begins to decrease simultaneously with the increase in liquid vitreous. • Subsequent PVD of the fellow eye w/in 2 years of the first eye 65-88%. Balazs EA, Denlinger JL: Aging changes in the vitreous. In: Aging and Human Visual Function, pp 45–57. New York, Alan R. Liss, 1982. UC BERKELEY RESIDENT FORUM JUNE 2013 37 6/11/2013 POSTERIOR VITREOUS DETACHMENT IN HEALTHY ADULTS PVD development is NOT acute, but rather a slow asymptomatic process until completion. 5 Stages leading from incomplete to complete PVDs: COMMON CAUSES OF VITREOUS HEMORRHAGE 1. Abnormal Vessels Diabetic retinopathy (31–54%) Neovascularization from branch/central retinal vein occlusion (4–16%) Sickle cell retinopathy (0.2–6%) • Stage 0: no PVD, posterior vitreous face firmly attached to the retina. Retinal arteriole macroaneurysm (0.6-7%) • Stage 1: focal perifoveal PVD: incomplete PVD localized in the perifovea, occurring in 1-3 quadrants Retinal tear (11–44%) • Stage 2: incomplete, perifoveal PVD across all quadrants. Posterior vitreous detachment without retinal tear (4–12%) • Stage 3: detached posterior vitreous face from the retina • Stage 4: complete PVD, detached posterior vitreous face with Weiss ring 2. Rupture of Normal Vessels Trauma (12–19%) Retinal detachment (7–10%) Terson’s syndrome (0.5–1%) • • Retinal ischemia leads to VEGF release and induces neovascularization on the anterior retinal surface between the posterior vitreous cortex and ILM. • Normal vitreous traction with eye movement can lead to tractional forces and rupture of these vessels . • Accelerated vitreous liquefaction and syneresis is more common in diabetic eyes even without retinopathy. The vitreous cortex is integrally involved in neovascularization by acting as a surface that is necessary for the cellular proliferation, migration, and organization of neovascularization to occur. Retinal Tear 30% Vein occlusion 11% Proliferative DR 32% Age-related macular degeneration (0.6–4%) Spraul CW, Grossniklaus HE. Major Review: Vitreous Hemorrhage. Surg Ophthalmol 42:3-39, 1997. MECHANISM OF VITREOUS HEMORRHAGE MECHANISM OF VITREOUS HEMORRHAGE Vessels or Abnormal New Blood Vessels Other 13% PVD w/o tear 8% 3. Blood From Adjacent Source Initial Stages of Posterior Vitreous Detachment in Healthy Eyes of Older Persons Evaluated by Optical Coherence Tomography Arch Ophthalmol. 2001;119(10):1475-1479. 1. Bleeding From Diseased Retinal PSR 2% MA 2% AMD 2% Bleeding From Diseased Retinal Vessels or Abnormal New Blood Vessels • Neovascularization may also affect the vitreous. - PVD occur adjacent to neovascularization - region of superotemporal vessels, temporal to the macula, and adjacent to the optic disc. • After partial PVD, blood may layer out - boat shaped hemorrhage Faulborn J, Bowald S: Microproliferations in proliferative diabetic retinopathy and their relation to the vitreous: Corresponding light and electron microscopic studies. Graefes Arch Clin Exp Ophthalmol 223:130, 1985 UC BERKELEY RESIDENT FORUM JUNE 2013 38 6/11/2013 MECHANISM OF VITREOUS HEMORRHAGE 2. Rupture of Normal Retinal Blood Vessels • During a PVD, vitreous traction on the retinal vasculature may compromise a blood vessel especially at firm vitreo-retinal attachments: • Vitreous Base > Posterior Lens > ONH > Macula > Retinal Vessels RESULTS • • Vitreous hemorrhage from a broken retinal blood vessel, with or without a retinal tear, occurs in 6-41% of patients with acute symptomatic PVD. • 24/36 eyes (67%) had at least 1 retinal break • 11/36 eyes (31%) had more than 1 retinal break • 88% of breaks located in the superior retina • 14/39 eyes (39%) had RRD repaired vitrectomy & scleral buckling • Additional 14/39 (39%) had vitrectomy for non-clearing hemorrhage • Vitreous hemorrhages in the setting of an acute symptomatic PVD should alert the doctor that the risk of a retinal breaks is 7095%. • Incidence of RD in eyes w/ a h/o of RD in contralateral eye was 75% CONCLUSION • 1-4 breaks; mean breaks 1.7 Acute, spontaneous, non-traumatic PVD with dense fundus-obscuring vitreous hemorrhage is associated with high incidence of retinal tears and detachments, which require prompt surgical intervention. MECHANISM OF VITREOUS HEMORRHAGE 3. Extension of Hemorrhage Through The Retina From Other Sources • All patients were examined at 6 weeks • Additional risk factors:patients with retinal or vitreal hemorrhage, or pigment in the anterior vitreous (tobacco dust/shaffer’s sign) on the initial exam were re-examined 2 weeks after initial presentation. UC BERKELEY RESIDENT FORUM JUNE 2013 • Extensive Subretinal hemorrhage precedes the appearance of vitreal blood. • Age-related Macular Degeneration and Choroidal Melanoma are the two most common underlying diseases. • Vitreous hemorrhage in Idiopathic Polypoidal Choroidal Vasculopathy (IPCV) has also been reported. • Ultrasonography shows a highly echogenic subretinal mass without any choroidal shadowing. If the hemorrhage becomes massive, a total hemorrhagic RD should be suspected. 39 6/11/2013 RARE COMPLICATIONS 1. Hemosiderosis Bulbi and Photoreceptor Toxicity • caused by iron toxicity as hemoglobin is broken down 2. Proliferative Vitreo-Retinopathy • 336 eyes with acute spontaneous PVD • 118 (35%) eyes had vitreous hemorrhage • • • • macrophages and chemotactic factors induce fibrovascular proliferation • cell-mediated contraction of these membranes causes tangential retinal traction, fixed retinal folds and subsequent retinal detachment 3. Ghost Cell Glaucoma 43% taking aspirin, clopidogrel, or warfarin 31% not taking these medications Retinal tears occurred in 46% w/ vitreous hemorrhages versus 27% of patients w/o vitreous hemorrhages. • red blood cells degenerate into smaller, khaki-colored, spherical, more-rigid cells and remain for months following the initial hemorrhage. • the ghost cells enter the anterior chamber after disruption of the anterior hyaloid surface: after accidental trauma, cataract extraction, or vitrectomy 4. Hemolytic Glaucoma CONCLUSION: patients taking aspirin, clopidogrel, or warfarin who develop an acute PVD are more likely to present with vitreous hemorrhage. No statistically significant association was found between the use of oral anticoagulants in patients with acute PVD and vitreous hemorrhage and the presence of retinal tears/detachments. MANAGEMENT AND TREATMENT • Free hemoglobin, hemoglobin-laden macrophages and red-blood cell debris can block the trabecular meshwork. • Clinically indistinguishable from ghost cell glaucoma MANAGEMENT AND TREATMENT 1. Establish the etiology and source of the vitreous hemorrhage 1. Observation • Unknown etiology and attached retina on scleral depressed exam and on ultrasonography • Rest with head elevated 30-45 degree angle • Re-evaluate after 3-7 days Observation Referral Referral Timing Acute PVD w/ small VH and w/o retinal tear on scleral depression Acute PVD w/ VH and identified retinal tear Urgent Acute PVD w/ VH and w/o retinal tear on ultrasonography Acute PVD w/ dense fundus obscuring VH Urgent VH secondary to PDR, CRVO/BRVO Non-urgent 2. Referral to retinal specialist VH secondary to RD, open globe injury, AMD, and IPCV UC BERKELEY RESIDENT FORUM JUNE 2013 Urgent 40 6/11/2013 MANAGEMENT AND TREATMENT Timing of Vitrectomy REFERENCES • Balazs EA, Denlinger JL: Aging changes in the vitreous. In: Aging and Human Visual Function, pp 45–57. New York, Alan R. Liss, 1982. • ETDRS report number 7. Ophthalmology 1991;98(5 Suppl):741–756. • Foos RY. Posterior vitreous detachment. Trans Am Acad Ophthalmol Otolaryngol. 1972;76:480-497. Gloor BP. The vitreous. In: Moses RA, Hart MH, editors. Adler's physiology of the eye: clinical applications. St Louis: CV Mosby, 1987:246–67. Retinal Detachment Urgent • Iris or Angle Neovascularization Urgent • Le Goff MM, Bishop PN. Adult vitreous structure and postnasal changes. Eye 2008; 22: 1214-1222 • Sarrafizadeh R, et al. Incidence of retinal detachment and visual outcome in eyes presenting with posterior vitreous separation and dense fundus-obscuring vitreous hemorrhage. Ophthalmology 2001; 108:2273-2278. Type 1 Diabetes One month • Schweitzer KD, et al. Predicting retinal tears in posterior vitreous detachment. Can J Ophthalmol 2011; 46:481-485. • Sebag J, Balazx EA: Morphology and ultrastructure of human vitreous fibers. Invest Ophthalmol Vis Sci 1989;30:1871 • Sebag J. Surgical anatomy of vitreous and the vitreoretinal interface. Duane’s Clinical Ophthalmology. 2006; Vol 6, Ch 51. • Sebag J. Vitreous Pathobiology. Duane’s Clinical Ophthalmology. 2006; Vol 3, Ch 39. • Spraul CW, Grossniklaus HE. Major Review: Vitreous hemorrhage. Surg Ophthalmol 1997 42:3-39. • Ruby AJ, Williams GA, Blumenkranz MS. Vitreous humor. Duane’s Clinical Ophthalmology. 2006; Ch 11. • Uchino E, Uemura A, Ohba N. Initial stages of posterior vitreous detachment in healthy eyes of older persons evaluated by optical coherence tomography. Arch Ophthalmol. 2001; 119:1475-1479 • Witmer MT, Cohen SM. Oral anticoagulation and the risk of vitreous hemorrhage and retinal tears in eyes with acute posterior vitreous detachment. J of Retina and Vitreous Diseases.2013; 33:621-626. Subhyaloid vitreous hemorrhage One month Type 2 Diabetes Two or three months Other Causes Three months or more ETDRS report number 7. Ophthalmology 1991;98(5 Suppl):741–756. Case PT 78 year old female EVAL AT THE SOCIETY FOR THE BLIND (SACRAMENTO) ON 1/2/2013 LV 2’ Bilateral Non-Exudative AMD I SPY WITH MY TELESCOPIC EYE: The Implantable Miniature Telescope for Age-Related Macular Degeneration Caitlin E. Walsh, O.D. University of California, Berkeley Edwin B. Mehr Low Vision Resident June 23, 2013 CC: Implantable Miniature Telescope Evaluation Visual difficulties: Reading books and newspaper, writing POHx: (-) H/o co-existing ocular disease, (-) H/o eye surgery TF refraction OD +1.00 -2.00 x090 OS +0.75 -1.00 x090 20/250-1 20/160+1 Contrast Sensitivity (Pelli-Robson) 5% Weber (2% Weber is normal) Confrontation Visual Fields (transilluminator) Full OD and OS UC BERKELEY RESIDENT FORUM JUNE 2013 BCVA Anterior Segment L/Ls Blepharitis OU Cornea Clear OU Iris Flat OU Lens Gr 3+ NS OU TA @ 10:45am 11mmHg, OS 12 mmHg Posterior Segment ONH Macula (C/D): 0.25/0.25 OU GA OD>OS, (-)CNV OU 41 6/11/2013 Age-Related Macular Degeneration Functional difficulties FDA approved July 1, 2010 Consequences Reading Recognizing faces Watching television Driving Self-care Social interaction The Implantable Miniature Telescope Increased risk of accidents More dependent on others Decreased quality of life Legal blindness Depression Indication Monocular implant 75 years or older Severe-profound vision loss End-stage macular degeneration 2.7x Fixed Focus Galilean Telescope Works in conjunction with the cornea Optimal focal distance of 3m Goal = Reduce the impact of the central scotoma IMT used for detailed tasks Un-operated eye used for safe travel Projects an enlarged image of the central field onto the retina Field of View OUT = 20-24 degree Field of View IN = 54 degrees 2.7x 54º 20º http://www.nei.nih.gov/health/maculardegen/armd_facts.asp www.centrasight.com The Implantable Miniature Telescope Visual effects 3.6mm (diameter) x 4.4mm (length), 13.5mm wide including haptics Biocompatible materials Implanted into the posterior chamber following phacoemulsification Protrudes 0.5 mm from the pupillary plane Prohibits binocular vision Modifications from standard phaco with foldable IOL implantation Retrobulbar block 12 mm limbal incision, 7 mm capsulorhexis Prophylactic peripheral iridectomy, 10 nylon sutures Colby et al. 2007. 13.5 mm www.centrasight.com Restricts peripheral vision Constricted to diameter of 20 degrees Reduced retinal illuminance Cost = 15,500 (covered by Medicare) 4.4 mm Visual confusion, diplopia or suppression Loss of depth perception Reduced contrast sensitivity 0.5 mm 4.4 mm = 13 IOLS! UC BERKELEY RESIDENT FORUM JUNE 2013 http://www.ocutech.com/bioptic-driving.aspx 42 6/11/2013 Centrasight TM Treatment Program CentrasightTM Treatment Program A treatment program for End-Stage AMD Retinal Specialist Diagnosis, surgical evaluation, pre and postoperative care Utilizes the Implantable Miniature Telescope Created by Isaac Lipshitz, M.D. Manufactured by VisionCare Ophthalmic Technologies (Saratoga, Ca) Requires a multidisciplinary approach Retinal specialist Corneal and Cataract specialist Low Vision Optometrist Occupational Therapist Occupational Therapist Demonstrates the External Telescope Simulator (ETS) Determines the patients preferred retinal locus Determines the eye to receive the prosthetic device Facilitates patching exercises prior to treatment Provides post-operative vision care VISUAL CRITERIA Severe to profound vision loss BCVA (20/160 – 20/800) Improvement in Vision with ETS Determines good surgical candidates Performs the surgery and post-op care DISEASE CRITERIA Geographic Atrophy or Disciform Scar Bilateral foveal involvement Provides eccentric viewing training ANATOMICAL CRITERIA Stable for at least 6 months No active CNV or Tx for CNV Baseline Endothelial Density 75-84 years old 2000 cells/mm2 85+ years old 1800 cells/mm2 Visually Significant Cataract > or = Grade 2 Anterior chamber depth > or = 3.0mm No co-existing ocular disease No anterior segment abnormalities No condition that could compromise the patient’s peripheral vision CentrasightTM Treatment Program Low Vision Optometrist Cornea and Cataract Specialist Initiates appropriate referrals Axial length > 21 mm Myopia < 6.0 D, Hyperopia < 4.0 D Phakic Gr 2+ NS, CS, or PSC Case PT 78 year old female EVAL AT THE SOCIETY FOR THE BLIND ON 1/2/2013 TF refraction OD +1.00 -2.00 x090 OS +0.75 -1.00 x090 BCVA 20/250-1 20/160+1 ETS 20/100 20/50 Provides post-operative vision rehabilitation FUNCTIONAL CRITERIA Realistic functional goals IMT will not restore the patient’s natural vision DOES NOT eliminate need for glasses and magnifiers Intraocular: 5 letter improvement Must tolerate loss of peripheral vision and with the ETS depth perception Interocular: 10 letter Must commit to working with the low vision improvement with the ETS optometrist and occupational therapist compared to the other eye following surgery without the ETS UC BERKELEY RESIDENT FORUM JUNE 2013 Reading Acuity using ETS over OS with +5.00D near cap Efficiency was 0.20/2.0M (16 pt font) Threshold was 0.20/1.25M (10 pt font Assessment Both eyes meet visual criteria Target OS for IMT prosthesis Plan Wear eye patch over OS 2-3 hrs/day while performing tasks of daily living Referred to the OT at the UC Davis Med Center 43 6/11/2013 Case GK 84 year old male Case GK 84 year old male EVAL AT THE SOCIETY FOR THE BLIND 1/2/2013 EVAL AT THE SOCIETY FOR THE BLIND 1/2/2013 CC: Glare and Diplopia Pre-op Trial Frame Refraction OD +0.75 -0.50x154 OS pl -0.25 x056 Post-op Trial Frame Refraction OD +3.25 -1.50 x060 OS +0.50 -0.50 x045 BCVA 20/400 20/500 ETS 20/100 BCVA 20/125 20/200 Reading acuity with a +5.00 D Add Efficiency Threshold 0.2/2.5M 0.2/1.6M Contrast Sensitivity (Pelli-Robson) OD 36% Weber and OS 6.3% Weber Assessment Good improvement in visual acuity with IMT OD Light sensitivity Reduced suppression of eye with IMT prosthesis Plan Released SV Distance SRx and SV Near SRx Recommended gray Cocoon fit-overs Recommended continued training with the occupational therapist to work on alternating fixation Confrontation Visual Fields Severely constricted <20 degrees 360 OD No restriction OS Conclusions Conclusions GOOD CANDIDATES FOR THE IMT POOR CANDIDATES FOR THE IMT • Meet anatomical and disease criteria • Previous intraocular surgery • Improvement in visual acuity with the external telescope simulator • Anterior segment abnormalities • Realistic goals and expectations • Constricted peripheral vision in un-operated eye • Willing to work with rehabilitation specialists • Prone to eye rubbing • Good chance of useful improvement in everyday activities • Cognitive impairment • Good chance of adjusting to change in vision UC BERKELEY RESIDENT FORUM JUNE 2013 44 6/11/2013 Conclusions Acknowledgments Careful patient evaluation, education, and selection are essential for a happy patient following surgery! Society for the Blind Richard Van Buskirk, O.D. Nancy Nguyen, O.D. Penny Riley, Clinic Coordinator IMT will not restore natural vision Glasses and magnifiers will still be necessary following surgery UC Berkeley School of Optometry Robert B. Greer, O.D. Marlena Chu, O.D. Ian Bailey, O.D. Cheyenne Huber, O.D. UC Davis Medical Center Time and effort required for post-surgical visual rehabilitation Jennifer Li, M.D. Mark Mannis, M.D. Terri Hayward, O.T. Colby et. al. 2007. Resources • • • • • • • • • • • • Brown, M. et al. Utility values associated with blindness in an adult population. Br J Ophthalmol2001;85:327-331. CATT Research Group, Martin DF, Maguire MG, Ying GS, Grunwald JE, Fine SL, Jaffe GJ. N Engl J Med. 2011 May 19; 364(20):1897-908. Colby KA et al. Surgical Placement of an optical prosthetic device for end-stage macular degeneration: the implantable miniature telescope. Arch Ophthalmol. 2007;125:1118-1112. Colucciello, M. The Merits and Limitations of the Implantable Miniature Telescope for AMD. Retinal Physician. 2010. http://www.retinalphysician.com/articleviewer.aspx?articleid=104846. Accessed April 28, 2013. FDA approval letter for Implantable Miniature Telescope. Food & Drug Administration Web Site. http://www.accessdata.fda.gov/cdrh_docs/pdf5/P050034a.pdf. Accessed February 18, 2013. Garfinkel, RA, Berinstein, DM, Frantz, BS. Treatment of Choroidal Neovascularization Through the Implantable Miniature Telescope. Am J Ophthalmol. 2006;141: 766-767. Haddrill, M. FDA-Approved Macular Degeneration Treatment. <Http://www.allaboutvision.com/conditions/amd-treatments.htm>. Haller, JA. A New Option for End-Stage AMD. Review of Ophthalmology. 2010. http://www.revophth.com/content/d/retinal_insider/c/25844/ Harvitt, DM. Lecture 1. Vision Science 203B. Spring 2013. Hudson et al. IMT-002 Study Group. Implantable miniature telescope for the treatment of visual acuity lossresulting from end-stage age-related maculard egeneration: 1 year results. Ophthalmology. 2006;113:1987-2001. Hudson et al. Implantable Telescope for End-stage Macular Degeneration: Long term Visual Acuity and Safety Outcomes. J Ophthalmol 2008;146:664–673. Lane. SS, Kuppermann, BD. The implantable miniature telescope for macular degeneration. Curr Opin Ophthalmol. 2006;17(1):94-98. Resources • • • • • • • • UC BERKELEY RESIDENT FORUM JUNE 2013 Lane, SS et al. A prospective multicenter clinical trial to evaluate the safety and effectiveness of the implantable miniature telescope. Am J Ophthalmol. 2004; 137:9931001. Rein, DB, Wittenborn, JS, Zhang, X, Honeycutt, AA, Lesesne, SB, Saaddine, J,. Forecasting Age-Related Macular Degeneration Through the Year 2050: The Potential Impact of New Treatments. Arch Ophthalmol. 2009;127 (4): 533-540. Rosner, M, Ben-Simon, G, Sachs, D. Feasibility and Safety of Laser Treatments in eyes with an Intraocular Implantable Miniature Telescope. J Cataract and Refractive Surgery.2003; 29:1005-1010. Singer, M et al. Pars plana posterior capsulotomy in a patient with a telescope prothesis for age-related macular degeneration. Arch Ophthalmol. 2010;128(8):1065-1067. VisionCare’s Implantable Miniature Telescope: An intraocular telescope for treating severe to profound vision impairment due to bilateral end-stage age-related macular degeneration. Patient Information Booklet. Saratoga: VisionCare Ophthalmic Technologies, Inc, 2010. Print. VisionCare’s Implantable Miniature Telescope: An intraocular telescope for treating severe to profound vision impairment due to bilateral end-stage age-related macular degeneration. Professional Use Information. Saratoga: VisionCare Ophthalmic Technologies, Inc, 2010. Print. Williams, R, Brody, BL, Thomas, RG, Kaplan, RM, Brown, SI. The Psychosocial Impact of Macular Degeneration. Arch Ophthalmol. 1998;116:514-520. Ying, GS, Maguire, M. Development of a Risk Score for Geographic Atrophy in Complications of the Age-Related Macular Degeneration Prevention Trial. Ophthalmology 2011;118:332–338. 45 6/11/2013 Keratoglobus PKP after KCN: the thick and thin of it Tarah Lee, OD VA Palo Alto Health Care System Primary Care and Low Vision Rehabilitation Resident Cirrus anterior segment OCT Pentacam images OD http://www.kerasoftic.com/en/eye‐care‐professional/educational/ OS http://benjamineye.com/sites/benjamineye.com/files/i mages/page/pentacam_hr_overview_display.jpg UC BERKELEY RESIDENT FORUM JUNE 2013 46 6/11/2013 PKP Procedure Indications for PKP • Anterior Cornea – Keratoconus (KCN) – Corneal Dystrophies – Trauma – chemical burns – Infections – scars – Stevens-Johnson Syndrome (SJS) – Ocular cicatricial pemphigoid (OCP) Hong Kong Med J. 2012 Dec;18(6):509‐16. Indications for PKP con’t Indications for PK • Posterior Cornea – Fuchs endothelial dystrophy – Bullous Keratopathy • Aphakic (ABK) • Pseudophakic (PBK) – Posterior polymorphous dystrophy (PPMD) – Corneal regraft http://openi.nlm.nih.gov/detailedresult.php?img=2880372_MEAJO‐17‐38‐g002&req=4 UC BERKELEY RESIDENT FORUM JUNE 2013 47 6/11/2013 PKP in KCN Early complications of PKP Suture problems Macular edema Primary graft failure Elevated IOP Wound leaks Persistent epithelial defects Filamentary keratopathy Choroidal hemorrhage Retinal detachment Hyphema Microbial keratitis Endophthalmitis • Immunological rejection rare • • • • • • • • • • • • Late complications of PKP Lamellar Keratoplasty • 10-20% of patients • Good visual outcomes • • • • • • • Late endothelial failure Unstable refractive endpoint Cataracts Glaucoma Graft rejection Epithelial downgrowth Transmission of infectious diseases UC BERKELEY RESIDENT FORUM JUNE 2013 Host Tissue Donor Tissue PLK Superior scleral pocket Posterior stroma, DM and endo DLEK Posterior corneal disc Posterior stroma, DM and endo DSEK Endothelium and Descement’s membrane stripped Posterior stroma, DM and endo DSAEK Endothelium and Descement’s membrane stripped Posterior stroma, DM and endothelium DMEK Descemet’s membrane and endothelium stripped DM and endothelium DALK DM and endothelium Epithelium to deep stroma 48 6/11/2013 Advantages and disadvantages of DALK vs. PKP DALK Advantages Disadvantages Eliminates risk of endothelial rejection More technically demanding Reduced endothelial cell loss Prolonged operative time Anticipated improved graft survival Astigmatism rates similar to PKP Largely extraocular procedure Risk of conversion to PKP Greater wound strength Double A/C, interface haze Less dependence on topical steroids Recurrence of stromal corneal dystrophies Earlier suture removal Contraindicated if stroma too thin or excessive DM striae Similar refractive error and BCVA http://www.revoptom.com/continuing_education/tabviewtest/lessonid/107933/ Corneal Collagen Cross-linking (CXL) Intracorneal Ring Segments (ICRS) • May slow progression of • PMMA segments KCN • May include epithelial http://www.shinagawa.com.sg/en/lasik-services/lasik-xtra • Flatten and reshape the debridement • Topical riboflavin • Implanted into stroma 370 um http://www.coastalvisionmedical.com/site/intacs.htm cornea • UV-A exposure at 370 um http://www.oocities.org/wallstreet/2124/KERAweb/CornealChange s.html http://www.revophth.com/content/i/1777/c/32329/ UC BERKELEY RESIDENT FORUM JUNE 2013 49 6/11/2013 Key Points References • • Penetrating keratoplasty (PKP) has been the mainstay of surgical treatment for corneal blindness • Many potential complications, though most are rare • Allograft rejection and late endothelial failure are the most common causes of graft failure • Regrafts are 3x as likely to fail as primary grafts • Increase in lamellar corneal transplants due to improved surgical techniques • Alternative treatments such as intracorneal ring segments and corneal collagen cross-linking are available • • • • • • • • • • • • • • • • Young AL, Kam KW, Jhanji V, Cheng LL, Rao SK. A new era in corneal transplantation: paradigm shift and evolution of techniques. Hong Kong Med J. 2012 Dec;18(6):509-16. Wang J, Hasenfus A, Schirra F, Bohle RM, Seitz B, Szentmáry N. Changing indications for penetrating keratoplasty in Homburg/Saar from 2001 to 2010--histopathology of 1,200 corneal buttons. Graefes Arch Clin Exp Ophthalmol. 2013 Mar;251(3):797-802. Stechschulte SU, Azar DT. Complications after penetrating keratoplasty. Int Ophthalmol Clin. 2000 Winter;40(1):27-43. Chan E, Snibson GR. Current status of corneal collagen cross-linking for keratoconus: a review. Clin Exp Optom. 2013 Mar;96(2):155-64 Jhanji V, Sharma N, Vajpayee RB. Management of keratoconus: current scenario. Br J Ophthalmol. 2011 Aug;95(8):104450. Cassidy D, Beltz J, Jhanji V, Loughnan MS. Recent advances in corneal transplantation for keratoconus. Clin Exp Optom. 2013 Mar;96(2):165-72. Reinhart WJ, Musch DC, Jacobs DS, Lee WB, Kaufman SC, Shtein RM. Deep anterior lamellar keratoplasty as an alternative to penetrating keratoplasty a report by the american academy of ophthalmology. Ophthalmology. 2011 Jan;118(1):209-18. Rabinowitz YS. Keratoconus. Surv Ophthalmol. 1998 Jan-Feb;42(4):297-319 Romero-Jiménez M, Santodomingo-Rubido J, Wolffsohn JS. Keratoconus: a review. Cont Lens Anterior Eye. 2010 Aug;33(4):157-66;. Tan DT, Dart JK, Holland EJ, Kinoshita S. Corneal transplantation. Lancet. 2012 May 5;379(9827):1749-61. Borderie VM, Sandali O, Bullet J, Gaujoux T, Touzeau O, Laroche L. Long-term results of deep anterior lamellar versus penetrating keratoplasty. Ophthalmology. 2012 Feb;119(2):249-55. Fares U, Sarhan AR, Dua HS. Management of post-keratoplasty astigmatism. J Cataract Refract Surg. 2012 Nov;38(11):2029-39. Tan DT, Por YM. Current treatment options for corneal ectasia. Curr Opin Ophthalmol. 2007 Jul;18(4):284-9. Claesson M, Armitage WJ. Clinical Outcome of Repeat Penetrating Keratoplasty. Cornea. 2013 Apr 12. Collagen-Crosslinking: asking the tough questions. Retrieved June 1, 2013. http://www.revophth.com/content/i/1777/c/32329/ CXL USA online. Retrieved June 1, 2013. http://www.cxlusa.com/default.aspx Ertan A, Muftuoglu O. Intracorneal ring segments for keratoconus. Expert Rev Ophthalmol. 2008;3(5):585-591. Chief Complaint: 81 year‐old male with painful red eye OS Scleritis: A Royal Pain in the Eye Jennifer M. Tu, OD San Francisco VA Medical Center Primary Care Exam Findings Right Eye VA cc 20/40 20/40 Lids/Lashes Collarettes 2+ Collarettes 2+, mucous 2+ LL Conjunctiva/Sclera Clear Injection 4+, small elevated nodule @sup‐temp under lid Cornea Trace KP Trace KP Ant Chamber Deep and quiet Deep and quiet 16 mm Hg IOP 16 mm Hg Lens NS 2+ NS 2+ Vitreous Syneresis Syneresis Optic Nerve: June 23, 2013 UC BERKELEY RESIDENT FORUM JUNE 2013 Left Eye Macula: Periphery: OD: 0.30 OS: 0.35 A: Nodular anterior scleritis OS Scattered small drusen 1+ OU, no CNV P: Begin ibuprofen 400 mg QID. No holes/tears/breaks OU B‐scan: Negative T‐sign Order lab tests (CBC, ESR, PPD, RPR, TP‐PA, ANA, ACE, ANCA, RF) 50 6/11/2013 Anatomy Differential Diagnosis • Conjunctivitis • Acute angle closure – Diffuse redness – Teary eyes, mucous discharge – Papillary vs follicular reaction – Elevated IOP with acute eye pain – Mid‐dilated pupil – Corneal edema hazy vision Episcleritis • Anterior uveitis* – – – – Pain with photophobia Circumlimbal flush Keratic precipitates Anterior chamber reaction Younger Older Onset Acute Insidious VA Unaffected Reduced VA Blood Vessels Sectoral superficial injection (bright red) Superficial and deep vessel injection (violaceous hue) Vessels blanch with phenylephrine Deep vessels do not blanch with phenylephrine No pain Severe, deep, boring Pain Blood Supply • • Derived from the anterior ciliary arteries which anastamose with the posterior ciliary arteries The sclera itself is an avascular structure 1. Conjunctival Plexus • Mobile with a cotton tip 2. Superficial Episcleral Plexus Composed of collagen, fibroblasts, and GAGs Extraocular muscles insert into the sclera Innervation by long and short ciliary nerves Blood supply derived from the anterior ciliary arteries Scleritis Age *May present with scleritis • • • • Conjunctiva Sclera Tenon’s space Episclera Pathophysiology of Scleritis • Histology studies show granulomatous lesion consisting of plasma cells, lymphocytes, and mast cells clinically manifesting as scleral inflammation Active T‐cell inflammatory response incited by trauma or infection Endothelial swelling of vessels and microvascular occlusion SCLERAL INFLAMMATION • Radial orientation of vessels 3. Deep Episcleral Plexus • Do not blanch with phenylephrine UC BERKELEY RESIDENT FORUM JUNE 2013 Collagen fibrils unravel due to alteration of proteoglycans Neutrophil infiltration of vessel wall 51 6/11/2013 Clinical Examination Checklist History External Exam Pain Onset (acute vs insidious) Evaluate in natural lighting Violaceous vs bright red hue Slit Lamp Exam Red free filter Corneal complications ‐ Marginal or interstitial keratitis Anterior chamber cell Posterior Segment Exudative retinal detachment B scan for fluid under Tenon’s capsule (T‐sign) Classification Types Diffuse Nodular Scleromalacia Perforans (Necrotizing without inflammation) Necrotizing with inflammation Anterior Posterior Scleritis Note: use an optic section to determine extent of edema and which layers are involved Diffuse Anterior Scleritis • Seen in 60% of cases • Rearrangement of collagen scleral fibers – resulting in blue hue • Systemic association in 45% of cases – Rheumatoid arthritis most common • Corneal findings – Peripheral infiltrates – Corneal thinning UC BERKELEY RESIDENT FORUM JUNE 2013 Nodular Anterior Scleritis • Seen in 20% of cases • May have multiple nodules present • Systemic association in 40 – 50% of cases – Commonly infectious origin • Underlying sclera may be transparent however no necrosis Firm, immobile, tender nodule typically found close to limbus 52 6/11/2013 Scleromalacia perforans Necrotizing with inflammation Posterior Scleritis (Necrotizing without inflammation) • • • • Lack of symptoms Severe atrophy of the episclera Yellow‐white infarcted tissue Associated with longstanding RA • White sclera due to capillary dropout • Infarction and necrosis of underlying sclera • Scleral edema extending outward around the globe (pictured below) • Inflammation occurs posterior to medial and lateral rectus muscle insertions • Less commonly associated with systemic disorders • Ocular complications • Uveitis • Retinal detachment • Proptosis and diplopia • Subretinal mass • Choroidal effusion Ocular Complications defined as the following: • Interstitial keratitis • Cataract • Marginal corneal ulcer • Vitritis • Anterior uveitis • Cystoid macular edema • IOP > 21 mm Hg • Exudative retinal detachment Decreased Vision 78% had pre‐existing systemic diagnosis Of 243 patients 44% of patients have an associated systemic condition Posterior Segment Findings 14% diagnosed after initial evaluation • None in episcleritis group • 16% in scleritis group Infectious (7%) Conversion to Bilateral Disease T‐sign = thickened sclera with fluid in Tenon’s space • Episcleritis: • Scleritis: Rheumatic (37%) 8% diagnosed during follow up period 12% at 1 year 24% at 1 year • Commonly seen in posterior scleritis • Infrequently associated with anterior scleritis UC BERKELEY RESIDENT FORUM JUNE 2013 Herpes zoster (4.5%) Rheumatoid arthritis (15.2%) Wegener’s Granulomatosis (+systemic vasculitides) Systemic lupus erythematosus 53 6/11/2013 Laboratory Testing Complete blood count (CBC) Complete metabolic panel (CMP) Antineutrophil cytoplasmic antibody (C‐ANCA and P‐ANCA) Antinuclear antibody (ANA) Angiotensin converting enzyme Fluorescent treponemal antibody absorption (FTA‐Abs) Rapid plasma reagin (RPR) Rheumatoid factor (RF) Purified protein derivative (PPD) Lyme antibody Lysozyme Chest x‐ray Take Home Points Treatment Options NSAID Oral corticosteroids Immunosuppressive drugs Initial drug of choice for non‐ necrotizing anterior scleritis Initial drug of choice for necrotizing anterior scleritis and posterior scleritis OR Failed NSAID therapy Necrotizing anterior scleritis OR Failed corticosteroid therapy OR Steroid related adverse events References 1. Akpek EK, Thorne JE, Qazi FA, Do DV, Jabs DA. Evaluation of patients with scleritis for systemic disease. Ophthalmology. 2004 Mar;111(3):501‐6. 2. Beardsley RM, Suhler EB, Rosenbaum JT, Lin P. Pharmacotherapy of scleritis: current paradigms and future directions. Expert Opin Pharmacother. 2013 Mar;14(4):411‐24. • Be able to recognize the clinical features in differentiating episcleritis from scleritis 3. Castells DD. Anterior scleritis: three case reports and a review of the literature. Optometry. 2004 Jul;75(7):430‐44. 4. Galor A, Thorne JE. Scleritis and peripheral ulcerative keratitis. Rheum Dis Clin North Am. 2007 Nov;33(4):835‐54, vii. 5. Nizam S, Johnstone A, Green M, Gough A. Necrotising scleritis and connective tissue disease‐‐three cases and a review. Clin Rheumatol. 2009 Mar;28(3):339‐41. • Scleritis is a severe ocular inflammatory disorder that may have systemic disease implications 6. Jabs DA, Mudun A, Dunn JP, Marsh MJ. Episcleritis and scleritis: clinical features and treatment results. Am J Ophthalmol. 2000 Oct;130(4):469‐76. 7. Jachens AW, Chu DS. Retrospective review of methotrexate therapy in the treatment of chronic, noninfectious, nonnecrotizing scleritis. Am J Ophthalmol. 2008 Mar;145(3):487‐492. 8. Raiji VR, Palestine AG, Parver DL. Scleritis and systemic disease association in a community‐based referral practice. Am J Ophthalmol. 2009 Dec;148(6):946‐50. • Urgent referral is warranted to initiate laboratory testing and possible systemic treatment of the underlying condition 9. Sainz de la Maza M, Molina N, Gonzalez‐Gonzalez LA, Doctor PP, Tauber J, Foster CS. Clinical characteristics of a large cohort of patients with scleritis and episcleritis. Ophthalmology. 2012 Jan;119(1):43‐50. 10. Sainz de la Maza M, Molina N, Gonzalez‐Gonzalez LA, Doctor PP, Tauber J, Foster CS. Scleritis therapy. Ophthalmology. 2012 Jan;119(1):51‐8. 11. Watson PG, Hayreh SS. Scleritis and episcleritis. Br J Ophthalmol. 1976 Mar;60(3):163‐91. 12. Wieringa WG, Wieringa JE, ten Dam‐van Loon NH, Los LI. Visual outcome, treatment results, and prognostic factors in patients with scleritis. Ophthalmology. 2013 Feb;120(2):379‐86. doi: 10.1016/j.ophtha.2012.08.005. Epub 2012 Nov 20. PubMed PMID: 23177360. UC BERKELEY RESIDENT FORUM JUNE 2013 54 6/11/2013 Not Always on Target TICKED OFF PATIENTS Ocular Manifestations of Lyme Disease Several countries 43 States California is considered an endemic area http://www.pbase.com/image/51179027 Ryan Johnson, OD Resident, Binocular Vision Clinic University of California, Berkeley June 23, 2013 Pathognomoic Seen in 50% of patients At risk after 24 hours http://hardinmd.lib.uiowa.edu/cdc/lymedisease6.html • Between 3 & 30 days • No later than 3 months • Erythema Migrans • Borrelial lymphocytoma • 6 months • Migrant muscle pain • Large joint pain • Bone pain 100% transmission by 3 days CDC Definition of Lyme Disease • Exposure in an endemic area • Erythema migrans within 30 days Dermatologic Musculoskeletal A Multisystem Disorder • • • • Exposure in an endemic area Erythema migrans absent Signs involving one organ system Positive laboratory test • Within several weeks • 4‐8% of patients • Atrioventricular blocks • Carditis • Highly variable • Months to years after • Bannwarth Syndrome • Encephalomyelitis • Cranial nerve palsies • No history of exposure • Erythema migrans present • Involvement of two organ systems Cardiac Neurologic • No exposure in an endemic area • Erythema migrans present • Positive serology UC BERKELEY RESIDENT FORUM JUNE 2013 55 6/11/2013 Documented Manifestations of Lyme Rough and Ready, California: 12yo • • • • • • • • • • • • • Blepharospasm Uveitis Panophthalmitis Chorioiditis Optic Disc Edema Macular Edema Pseudotumor Cerebri Optic Neuritis AION Temporal Arteritis Optic Atrophy Horner’s Syndrome Argyll-Robertson Pupil STAGE 3: Late/Immunologic • Conjunctivitis • Periorbital Edema STAGE 2: Dissemination STAGE 1: Infection • Diagnosed with active neuro‐lyme disease 2011 • • • • • • Nerve Palsies Stromal Keratitis Episcleritis Scleritis Orbital Myositis Cortical Blindness – Confirmed with ELISA and Western Blot – Presumed contracted at 6yo (2007) • Lyme‐associated arthritis in both knees • Presenting Complaints: – – – – Photophobia Floaters Midline Shift Tracking Difficulties Mechanisms of TBI and Visual Consequences in Military and Veteran Populations Optometry & Vision Science February 2013 • 65% ‐ Reported visual problems • 50% ‐ Reading problems • Light Sensitivity – 67% of blast related – 33% of non‐blast related • Convergence insufficiency • Accommodative dysfunction • Oculomotor anomalies • Ocular Inflammation – Keratitis – Anterior Uveitis – Intermediate Uveitis http://directorsblog.health.azdhs.gov/?p=3493 UC BERKELEY RESIDENT FORUM JUNE 2013 56 6/11/2013 Perceptual Difficulties Ocular Motility San Jose, California: 19yo • Diagnosed in 2011 • Smooth Pursuits & Integration • Fast & Accurate Saccades • No Midline Hesitation – No associated tick bite – Presumed contracted at 15yo (2010) – Stage 3 DEM • Difficulties with Rapid Automatic Naming • Adequate Spatial Planning and Tracking Skills PMA‐PS • Presenting Complaints: – Diplopia; Intermittent at distance – “Jerky Tracking” – Intermittent blurry vision • Reduced Visual Processing Speed TVAS • Spatial Planning Difficulties Cranial Nerve Literature Cranial Nerve 6 Palsy • Lacomte ‐ 1989 • Esophoria; DI • Increases in lateral gaze • OS: Abduction restriction Ocular Posture Ocular Motility Abducens palsy Paralytic sixth nerve palsy ◦ Most common cause of diplopia Symptomatic for 10 years UC BERKELEY RESIDENT FORUM JUNE 2013 ◦ Diplopia Absence of adduction restriction 2 week treatment protocol ◦ 200mg doxycycline per day • Divergence difficulties Facial palsy most common MRI showed inflammation of: Bilateral: CN 3,7,9,10,11,12 Unilateral: 4,5,6 Collegium Antropologicum 2005 ‐ Zrinsnak ◦ Rules out nuclear lesion Vergence • Diplopia during binocular facility – – – – Clinical Infectious Disease 2009 ‐ Sauer Accommodation • Van Erp ‐ 2011 – Facial palsy most common • 2/3 unilateral, 1/3 bilateral – Usually during second month of disease – Oculo‐motor nerve also described or ◦ Headaches Strabismus surgery ◦ Initial 40pD esotropia ◦ Post‐Op: 10pD esotropia ◦ 2g ceftriaxone per day ◦ Unable to abduct Resolution at 2 ‐12 weeks ◦ Diplopia remained Resolution through 7 years 57 6/11/2013 Tuolumne, California: 29yo Diagnosing Convergence Palsy • Diagnosed in 2010 • Diplopia • jj – When watching TV or reading – Horizontal – 6 months • Arthritis • “Brain fog” – Changes in memory – Clumsy – Changes in cognitive functioning • Versions • Ductions Ocular Motility Ocular Posture • R‐AX(T) • Divergence • Convergence • NPC Vergence • Headaches Seeing Through The Brain Fog DEM PMA‐PS • Difficulties with Rapid Automatic Naming • Adequate Spatial Planning and Tracking Skills • Reduced Visual Processing Speed UC BERKELEY RESIDENT FORUM JUNE 2013 Readalyzer • Increased Number of Fixations • Prolonged Fixation Duration • Reduced Reading Rate Denali National Park, Alaska: 37yo • Diagnosed with Lyme disease in 2012 • Suspected present for more than 10 years • Presenting Complaints: – Asthenopia & fatigue with reading – Auditory processing easier than visual processing 58 6/11/2013 Lyme Disease as an Acquired Brain Injury Perceptual Difficulties Ocular Motility DEM Variability of Presentation Light Sensitivity Convergence Insufficiency & Palsy Cranial Nerve Palsies Visual Perceptual Difficulties • Pursuits: Saccadic Intrusions • Saccades: Hypometric • Difficulties with Rapid Automatic Naming • Adequate Spatial Planning and Tracking Skills References • • • PMA‐PS • Reduced Visual Processing Speed • • • • Readalyzer • Increased Number of Fixations • Prolonged Fixation Duration • Reduced Reading Rate • • • • • Biesiada, Grazyna et al. “Lyme Disease: Review.” Archives of Medical Science. 6 (2012): 978‐82. Fatterpekar, Girish et al. “Orbital Lyme Disease: MR Imaging Before and After Treatment: Case Report.” American Journal of Neuroradiology. 23 (2002): 657‐9. Goodrich, GL et al. “Mechanisms of TBI and Visual Consequences in Military and Veteran Populations.” Optometry & Visual Science. 90.2 (2013): 105‐12. Huppertz, Hans‐Iko et al. “Ocular Manifestations in Children and Adolescents With Lyme Arthritis.” British Journal Ophthalmology. 83.11 (1999): 1149‐52. Lecomte, F et al. “Neurological Maifestations of Lyme Disease and Treatments.” Biomedical and Pharmacotherapy. 43 (1989): 409‐413. Mikkila, Helena et al. “The Expanding Clinical Spectrum of Ocular Lyme Borreliosis.” Ophthalmology. 107.3 (2000): 581‐87. Mora, Paolo and Carta, Arturo. “Ocular Manifestations of Lyme Borreliosis in Europe.” International Journal of Medical Sciences. 6.3 (2009): 124‐ 125. Sauer, Arneud et al. “Five Cases of Paralytic Strabismus as a Rare Feature of Lyme Disease.” Clinical Infectious Diseases. 48 (2009): 756‐9. Sperling, J et al. “Evolving Perspectives on Lyme Borreliosis in Canada.” The Open Neurology Journal. 6 (2012): 94‐103. Van Erp, Willemijn et al. “Opsoclonus and Multiple Cranial Neuropathy as a Manifestation of Neuroborreliosis.” Neurology. 77 (2011): 1013‐14. Winterkorn, Jacqueline. “Lyme Disease: Neurologic and Ophthalmic Manifestations.” Survey of Ophthalmology. 35.3 (1990): 191‐204. Zrinsnak, Ognjen et al. “Paralytic Strabismus as a Manifestation of Lyme Borreliosis. Coll Anthropology. 29 (2005): 137‐9. Nothing but Net: Choroidal Neovascular Membranes for the Primary Care Optometrist Jillian F. Meadows, OD, MS San Francisco VAMC June 23, 2013 RFV: temporally associated with getting “dust in eye” while driving two days ago Ocular Hx: VAsc (cPH) MRx Pupils Ant Seg Health Ta (Tonosafe) ONH UC BERKELEY RESIDENT FORUM JUNE 2013 Case Presentation 63 y/o HM presented with decreased vision OD, CE/PCIOL 1999 OU OD OS 20/150‐ (NI) 20/30+ (20/20) NI ‐‐ ERRL, (‐)APD ERRL, (‐)APD WNL WNL 16 16 0.35, full pink rim 0.35, full pink rim Macula See photo Flat, clear Post Seg Health See photo 1 intraretinal flame hemorrhage, round hypopigmented area nasal to fovea 59 6/11/2013 Case Presentation Case Presentation Presumed idiopathic choroidal neovascular membrane Cardinal Signs of CNV Pigment epithelial detachment Cardinal Signs of CNV Cystoid macular edema Subretinal fluid Irregular elevation of RPE UC BERKELEY RESIDENT FORUM JUNE 2013 60 6/11/2013 Cardinal Signs of CNV Subretinal and intraretinal Lipid exudation Differential Diagnosis of CNVM hemorrhage Idiopathic Exudative AMD Excessive photocoagulation Choroidal rupture Polypoidal CNVM Choroidal tumors Macular Telangiectasia Pathologic myopia Normal Vasculature Development All organs except the brain and kidney are vascularized via vasculogenesis. Angioid streaks CSCR POHS Embryologic Vasculature Development Vasculogenesis Angiogenesis Vasculogenesis: Local precursor cells differentiate into endothelial cells, which subsequently join to form vessels Angiogenesis: Blood vessels sprout from existing vessels and penetrate adjacent tissue The retina is vascularized by both vasculogenesis and angiogenesis. Highly coordinated process involving VEGF, its receptors, and other growth factors Final “maturation” process allows vessels to recruit pericyte support and develop structural integrity, facilitated by PDGF, Ang1, Ang2, TGF‐β1. Copyright © 2001, European Society of Cardiology Conway E M et al. Cardiovasc Res 2001;49:507-521 UC BERKELEY RESIDENT FORUM JUNE 2013 All mediated by VEGF (and friends) 61 6/11/2013 VEGF and Whom? Vascular Endothelial Growth Factor Family • Glycoproteins • VEGF‐A, ‐B, ‐C, ‐D, ‐E • Placental Growth Factor (PlGF) Pathologic Vasculature Development Unregulated angiogenesis that lacks maturation into vessel competency, resulting in leaky vessels of poor integrity Produced by RPE, Müller cells, pericytes, endothelial cells, and ganglion cells Normal Functions: • Promotes proliferation, migration, and capillary tube formation…but not maturation • Increases vascular permeability Stimuli: • Normal physiology (including trophic maintenance of choriocapillaris) • Hypoxia • Inflammation? • Structurally sound • Targeted direction • Visually necessary • Bruch’s deposits • CNV in choroiditis • But not all choroiditides cause CNV vs. Hypoxia • Diffuse thickening of Bruch’s • But not all CNVs due to hypoxia Prevailing theories Disruption of Bruch’s Membrane Altered RPE and ECM metabolism UC BERKELEY RESIDENT FORUM JUNE 2013 • Incompetent • Invasive, lacking taxis • Visually destructive Recent paradigm shift Probably not… Inflammation Pathologic Very delicate homeostasis… So what tips the balance? Are all CNVMs created equal? Choroidal neovascularization is poorly characterized and poorly understood. V E G F Surgical CNVM excision Macular translocation Anti‐inflammatory Triamcinolone Ablative Laser photocoagulation Photodynamic therapy Molecular (Anti‐VEGF) Macugen (pegaptanib) Lucentis (ranibizumab) Avastin (bevacizumab) 62 6/11/2013 Latest therapeutic agents VEGF Trap (aflibercept) • FDA approved for exudative AMD • High affinity to most members of VEGF family, including PlGF • Less frequent dosing schedule than current anti‐ VEGF meds • Efficacy comparison to Lucentis still ongoing… Patient Update RNA Interference • Bevasirinib – Inhibition of VEGF through RNA interference – Upstream mechanism causes delayed onset of activity; not superior to current meds • AGN211745 (Sirna‐027) – Inhibition of VEGFR‐1 through RNA interference – Studies ongoing BCVA: 20/150 to 20/80 s/p Avastin x 3 Clinical Pearls • Know the clinical signs that signal presence of CNVM: – PED, RPE irregularity, subretinal fluid, CME, lipid exudation, and subretinal hemorrhage • VEGF is only one of likely many inciting factors that can initiate CNVM, and not all CNVMs are created the same. • Long‐term blockade of VEGF may accelerate choriocapillaris atrophy. Other therapeutic mechanisms need to be discovered. UC BERKELEY RESIDENT FORUM JUNE 2013 References • • • • • • • • Do DV. Detection of new‐onset choroidal neovascularization. Curr Opin Ophthalmol. 2013 May;24(3):244‐7. PubMed PMID: 23518615. Do DV, Gower EW, Cassard SD, Boyer D, Bressler NM, Bressler SB, Heier JS, Jefferys JL, Singerman LJ, Solomon SD. Detection of new‐onset choroidal neovascularization using optical coherence tomography: the AMD DOC Study. Ophthalmology. 2012 Apr;119(4):771‐8. PubMed PMID: 22297028. Kinnunen K, Ylä‐Herttuala S. Vascular endothelial growth factors in retinal and choroidal neovascular diseases. Ann Med. 2012 Feb;44(1):1‐17. PubMed PMID: 21284527. Qazi Y, Maddula S, Ambati BK. Mediators of ocular angiogenesis. J Genet. 2009 Dec;88(4):495‐515. PubMed PMID: 20090210; PubMed Central PMCID: PMC3306772. Campochiaro PA. Retinal and choroidal neovascularization. J Cell Physiol. 2000 Sep;184(3):301‐10. PubMed PMID: 10911360. Spaide RF. Choroidal neovascularization in younger patients. Curr Opin Ophthalmol. 1999 Jun;10(3):177‐81. PubMed PMID: 10537776. D'Amore PA. Mechanisms of retinal and choroidal neovascularization. Invest Ophthalmol Vis Sci. 1994 Nov;35(12):3974‐9. PubMed PMID: 7525506. Gass JM. Stereoscopic Atlas of Macular Diseases. 3 ed. Klein EA editor. St. Louis, Missouri: Mosby; 1987. 63 6/11/2013 Myopia Prevalence1 Pediatric Myopia Modulation Alex J Smith, OD, FAAO Diplomate, American Board of Optometry UC Berkeley Dr. Michael G Harris Contact Lens Resident Increasing prevalence of myopia Risks of high myopia • “Myopia has reached epidemic proportions.”3 – Ophth Physiol Optics. September 2005 • Public Health Ramifications3,4 • Taiwanese schoolchildren2: – – – – Year 2000: 84% 16‐18 yr olds myopic Year 1983: 74% 16‐18 yr olds myopic Year 2000: 21% High (>6.00D) myopia at 18 yrs old Year 1983: 10.9% High (>6.00D) myopia at 18 yrs old UC BERKELEY RESIDENT FORUM JUNE 2013 – – – – – – – – – – Retinal detachment POAG Maculopathy Disc anomalies Lacquer cracks/CNVM Macular hole Staphyloma Cataracts Reduced visual quality Lifetime $ for treatment 64 6/11/2013 Peripipheral Hyperopic Defocus vs. Lag of accommodation • In both cases, light is focused behind the retinal plane CLAMP STUDY5 • RGPs for Myopia Control – Not effective • Peripheral hyperopic defocus – When optical correction is in place, central rays focus centrally – Peripheral rays focus behind the retina • No plus in it • Lag of accommodation – Transient central hyperopic defocus – Higher levels of education associated with myopia COMET Study 20036 • +2.00 add PAL – Small area of plus power • Overall 0.20 D difference (14%) over 3 years 2008 OEP Northwest Congress • Aller & Wildsoet twin study7 – Acuvue bifocal (putting plus on it) – Statistically significant but “not clinically significant” – Occurred in first year • Higher efficacy if high lag of accommodation + lower baseline myopia – 0.48 D difference • Highest efficacy if high lag of accommodation + eso – 0.64 D difference UC BERKELEY RESIDENT FORUM JUNE 2013 65 6/11/2013 Image shell8 Image shell ‐ Orthokeratology 9 LORIC STUDY 200510 2008 OEP Northwest Congress • Atropine intervention – Chua 200611 UC BERKELEY RESIDENT FORUM JUNE 2013 66 6/11/2013 COMET 2 Study 201112 • 0.28 D 3‐year difference Cambridge Anti‐Myopia Study 201313,14 • “Peripheral Refractive Changes Associated with Myopia Progression” IOVS Feb 2013 • No difference in myopic progression between any arm • No plus power (myopic defocus) applied to retina Hiraoka et al 201215 Reduced concentrations of Atropine • Chia et al 201216 UC BERKELEY RESIDENT FORUM JUNE 2013 67 6/11/2013 What can any OD do for Patients Tomorrow? • Atropine 0.1% References • • – Best balance of efficacy vs. side effects – 0.01% minimal side effects for similar efficacy to O‐K, MF soft • Orthokeratology – Topographer needed – Overnight lens wear risks • Multifocal soft contact lenses – Distance center has most evidence • Executive bifocal glasses with 3^BI • • • • • • • • • • • • • When in doubt... • • 1. Santodomingo, J. “Controlling Myopia Progression in Children” Menicon Horizons. 2011 May; 6. 2. Lin, LLK et al. “Prevalence of Myopia in Taiwanese Schoolchildren: 1983‐2000.” Annals Academy of Medicine. 2004 Jan;33(1):27‐33. 3. Saw, S‐M, et al. “Myopia and associated pathological complications.” Ophthal Phys Optics. 2005 Sept;22(5):381‐391 4. Kanski, Jack J. Clinical Ophthalmology. 5th Ed. Butterworth‐Heinemann. 2003 5. Walline, Jeffrey J et al. “A Randomized Trial of the Effects of Rigid Contact Lenses on Myopia Progression.” Arch Ophthalmol. 2004;122:1760‐1766. 6. Gwiazda, Jane. “Treatment Options for Myopia.” Optom Vis Sci. 2009 June;86(6):624‐628 7. Aller, TA. “Myopia Progression in a Twin Pair with Bifocal Soft Contact Lenses – Second Year Results After Single Crossover.” <http://www.aaopt.org/Submission/Search/SubmissionViewer.asp?SID=4203&BR=SP> 8. Smith, E. “Prentice Award Lecture 2010: A Case for Peripheral Optical Treatment Strategies for Myopia.” Optom Vis Sci. 2011 Sept;88(9):1029‐1044. 9. Herzberg, C. “An Update on Orthokeratology.” Contact Lens Spectrum; 2010 Mar. http://www.clspectrum.com/articleviewer.aspx?articleid=103967 10. Cho, P et al. “The longitudinal orthokeratology research in children (LORIC) in Hong Kong: a pilot study on refractive changes and myopic control.” Curr Eye Res. 2005 Jan;30(1):71‐80. 11. Chua, WH et al, “Atropine for the treatment of childhood myopia.” Ophthalmology. 2006 Dec;113(12):2285‐91. 12. PEDIG. “Progressive‐Addition Lenses vs. Single‐Vision Lenses for Slowing Progression of Myopia in Children with High Accommodative Lag and Near Esophoria.” IOVS. 2011 April;52(5):2749‐2757 13. Radhakrishnan, H. et al. “Peripheral Refractive Changes Associated with Myopia Progression.” IOVS. 2013 Feb;54(2):1573‐81 14. Allen, PM. Et al. “Aberration Control and Vision Training as an Effective Means of Improving Accommodation in Individuals with Myopia.” IOVS. 2009 Nov;50(11):5120‐5129. 15. Hiraoka, T. et al, “Long‐Term Effect of Overnight Orthokeratology on Axial Length Elongation in Childhood Myopia: A 5‐ Year Follow‐Up Study.” IOVS. 2012 June;53(7):3913‐3919 16. Chia, A. et al. “Atropine for the treatment of Childhood Myopia: Safety and Efficacy of 0.5%, 0.1% and 0.01% Doses (Atropine for the Treatment of Myopia 2).” Ophthalmology. 2012 Feb;119(2):347‐354. Primary Ocular HSV • Subclinical in 94% Re‐thinking HSV Keratitis • Bimoidal distribution – Ages 1‐5; Ages 13‐25 • Lid vesicles or erosive blepharitis (34‐ 44%) Andrea De Souza, O.D. Primary Care and Contact Lens Resident UC Berkeley School of Optometry UC BERKELEY RESIDENT FORUM JUNE 2013 • Epithelial keratitis (15‐63%) • Follicular or pseudomembraneous conjunctivitis (54‐84%) 68 6/11/2013 Unilateral or Bilateral? HSV Epithelial Keratitis • 50‐80% ocular HSV • Souza: 98% unilateral • Three types: • Wilhelmus: 97% unilateral – Bilateral HSV is undefined – Bilateral herpetic keratitis: presence of dendritic or geographic epithelial ulceration – Stellate – Dendritic (9‐15%) – Geographic • Brandt: 88.2% unilateral • Rezende:87.8% unilateral • Darougar: 81% unilateral – Bilateral herpetic keratitis: any form of HSV keratitis Management: Gold Standard • Orals: – 400mg Acyclovir 5x/d – 500mg Valacyclovir TID – 250mg Famciclovir TID • Topicals: – 1% Trifluridine 9x/d – 0.15% Gancyclovir 5x/d 1% Trifluridine (Viroptic) • Thimerosol preservative – – – – Corneal toxicity (punctate keratopathy) Burning or stinging (4.6%) Corneal edema Conj. edema, hyperemia • Compliance? • Consumer availability? • Cost: ~$100 (7.5mL) UC BERKELEY RESIDENT FORUM JUNE 2013 69 6/11/2013 0.15% Gancyclovir Gel (Zirgan) BAK preservative ◦ Irritation (20%) ◦ SPK (5%) ◦ Hyperemia (5%) Compliance? Cost: ~$170 (1 tube, 5gm) Oral and/or Topical Acyclovir Topical Steroids? • Stromal keratitis and endotheliitis? Yes. • Epithelial keratitis? NO! • Complications: – Enlargement of stellate lesions or dendrites – Progression to necrotizing stromal keratitis – Iritis or hypopyon – Secondary GLC Photo OD vs OMD Management • HEDS 2: Trifluridine and 400mg acyclovir – no benefit in preventing stromal keratitis or iritis • Collum L.: 3% acyclovir ophthalmic ointment vs. 400mg oral acyclovir – no statistically significant difference in the median time to healing UC BERKELEY RESIDENT FORUM JUNE 2013 Group 1: OD Group 2: OMD without cornea fellowship Group 3: OMD with cornea fellowship 70 6/11/2013 Pros: ‐ ‐ Topical Antivirals ‐ Easier to administer Lower systemic penetration Costly ‐ Trifluridine: $100 ‐ Gancyclovir: $170 Cons: ‐ ‐ ‐ Frequent dosing (trifluridine) Greater ocular side effects Refrigeration (trifluridine) Oral Antivirals Pros: Cons: ‐ ‐ ‐ ‐ ‐ ‐ ‐ Less frequent dosing Fewer side effects ‐ Metabolized by kidneys No refrigeration Cost ‐ Acyclovir: $20 ‐ Valacyclovir: $200 Reduces systemic viral load Penetrates multiple ocular tissues Difficult to swallow Alternative Management Oral Antivirals Pros: Cons: ‐ Less frequent dosing ‐ Fewer side effects ‐ Difficult to swallow ‐ Metabolized by kidneys ‐ No refrigeration ‐ Cost ‐ Acyclovir: $20 ‐ Valacyclovir: $200 ‐ Reduces systemic viral load ‐ Penetrates multiple ocular tissues Fluoroquinolones for HSV • Primary or recurrent HSV: – 800mg Acyclovir 5x/d (10 days) • Faster healing time • No increased side effects • DNA‐topoisomerase cleavage complexes • Structural similarities between topoisomerases of DNA viruses and bacteria • HSV 1 and 2: – dsDNA virus – uses topoisomerase I & II UC BERKELEY RESIDENT FORUM JUNE 2013 71 6/11/2013 African Swine Fever Virus: Method: No viral genome fragmentation observed Proposed MOA: ASFV topoisomerase II inhibitor DNA encodes for topoisomerase II inject animal cells with 30 fluoroquinolones at varying times after infection interference with ATPase activity torsional/replicative stress reduction in viral DNA replication and protein synthesis No viral genome fragmentation observed Proposed MOA: ASFV topoisomerase II inhibitor interference with ATPase activity torsional/replicative stress reduction in viral DNA replication and protein synthesis Reviewing Differentials Can fluoroquinolones have a similar effect on HSV? HSV Epithelial Keratitis Microbial Keratitis Unilateral or bilateral Unilateral Stellate lesions • multiple, elevated Infiltrate/ulcer • single, excavated Greater corneal or lid edema Can fluoroquinolones temporarily reduce host cell replication? UC BERKELEY RESIDENT FORUM JUNE 2013 Tx: antivirals Tx: antibiotics 72 6/11/2013 Reviewing Differentials HSV Epithelial Keratitis Infiltrative Keratitis Unilateral or bilateral Unilateral or bilateral Stellate lesions • multiple, elevated, irregular shape Pinpoint lesions • multiple, flat, round References • • • • Greater corneal or lid edema Tx: antivirals Tx: steroids • • • • • • • • • • • • • • UC BERKELEY RESIDENT FORUM JUNE 2013 National Eye Institute. “Herpetic Eye Disease Study (HEDS 1/2)”. U.S. National Institutes of Health. Sept 1999. Bernstein, D. et al. “Epidemiology, Clinical Presentation, and Antibody Response to Primary Infection With Herpes Simplex Virus Type 1 and Type 2 in Young Women”. Clinical Infectious Diseases. February 1, 2013; 56(3):344–51 Souza, P. et al. “Bilateral Herpetic Keratoconjunctivitis”. American Academy of Ophthalmology. March 2003. Vol 110, Num. 3, Pgs. 493‐496. Remeijer, L. et al. “Human herpes simplex virus keratitis: the pathogenesis revisited”. Ocular Immunology and Inflammation – 2004, Vol. 12, No. 4, pp. 255–285 Saini, J. and Argawala, R. “Clinical Pattern of Recurrent Herpes Simplex Keratitis”. Indian Journal of Ophthalmology. 1999. Vol: 47, Issue:1. Pg 11‐14. Wilhelmus, K. “Bilateral herpetic keratitis”. British Journal of Ophthalmology, 1981, 65, Pgs. 385‐387. Liesegang, L. “Herpes Simplex Virus Epidemiology and Ocular Importance”. Cornea (2001). 20(1): 1–13, 2001. Sacks, S. et al. “Clinical Management of Herpes Virus”. IOS Press. Netherlands. 1995. Pg. 23 Darougar, S. et al. “Epidemiological and clinical features of primary herpes simplex virus ocular infection”. British Journal of Ophthalmology, 1985, 69, Pgs. 2‐6. Farooq, A. and Shukla, D. “Herpes Simplex Epithelial and Stromal Keratitis: An Epidemiologic Update”. Survey of Ophthalmology. October 2012. Vol. 57, Number 5, Pgs. 448‐461. Potter, W. “An Overview of Ocular Herpetic Disease”. Review of Optometry. May 2010. Thygeson, P. et al. “The Unfavorable Response of Topical Steroid Therapy on Herpetic Keratitis”. Transactions of the American Ophthalmological Society. 1960; 58: 246–256. Kimura, S. et al. “Herpes Simplex Keratitis: An Experimental Study”. Investigative Ophthalmology. April 1962. Pgs 273‐278. Lee. S. and Pavan‐Langston, D. “Role of Acyclovir in the Treatment of Herpes Simplex Virus Keratitis”. International Ophthalmology Clinics. 1994. Volume 3, Issue 3. Pgs 9‐18. Collum, L. et al. “Oral Acyclovir (Zovirax) in Herpes Simplex Dendritic Corneal Ulceration”. British Journal of Ophthalmology. 1986; 70. Pgs 435‐438. Mottola, C. et al. “In Vitro Antiviral Activity of Fluoroquinolones Against African Swine Fever Virus”. Veterinary Microbiology. 2013. Pgs 1‐9. Bapat, A. et al. “Studies on DNA Topoisomerases I and II in Herpes Simplex Virus Type 2‐ infected Cells”. Journal of General Virology.1987. Vol. 68. Pgs 2231‐2237. Ebert, S. et al. “Topoisomerase II Cleavage of Herpes Simplex Virus Type1 DNA In Vivo Is Replication Dependent”. Journal of Virology. Sept. 1990. Vol. 64, No.9. Pgs 4059‐4066 73
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