Faculty Bibliography

Purpose To assess the cone photoreceptor mosaic in acute macular neuroretinopathy(AMN) using adaptive optics(AO) imaging. Methods Four consecutive patients with AMN were evaluated by dilated funduscopic examination, near-infrared reffectance(IR), confocal scanning laser ophthalmoscopy(SLO), eye-tracked spectral-domain optical coherence tomography(SDOCT) and a flood-illuminated retinal AO camera. Correlations were made between IRSLO, SDOCT and AO images at baseline and follow-up in 3 patients. Microperimetry was performed and correlated with SDOCT and AO images in 1 patient. Results At presentation, the cone photoreceptor density was decreased at the level of the AMN lesions in AO images in all patients. The cone photoreceptor mosaic disruption was more widespread than the lesion detected by IRSLO and SDOCT. At complete resolution of the AMN lesion in IRSLO, there was incomplete recovery of cone photoreceptor mosaic in AO. In 2 cases, there was persistent cone damage in AO despite restoration of the ellipsoid zone integrity on SDOCT at last follow-up. The area of disruption in cone mosaic revealed characteristic appearance of RPE cells in AO and correlated well with both SDOCT and microperimetry findings. Conclusions Cone photoreceptor damage and reconstitution were documented in vivo at the cellular level in AMN using AO imaging. AO appeared more sensitive than combined IRSLO and SDOCT to detect and follow photoreceptor damage in AMN patients. There was some irreversible cone photoreceptor damage in the 4 patients evaluated

PURPOSE:: To describe the clinical characteristics and progression of patients with multifocal choroiditis lesions who had minimal or no evidence of anterior uveitis and/or vitritis. METHODS:: Retrospective, observational, single-center consecutive case series. Clinical histories, examination, and multimodal imaging findings were analyzed. RESULTS:: Sixty-five eyes of 41 patients were identified. The mean age at diagnosis was 38.4 years (median, 35 years; range, 15-81 years), and 70.7% of the patients were women. Involvement was bilateral in 21 patients (51.2%) at presentation. The 60-month bilateral event-free survival was 75.0% (95% confidence interval, 49.8-91.2%). The mean visual acuity was 20/46 (median, 20/25; range, 20/20 to count fingers at 2 feet) at presentation and 20/42 (median, 20/25; range, 20/20-5/400) at the last recorded visit. The 60-month "20/50 or worse" event-free survival was 100%. Between the first presentation and final follow-up (a mean duration of 92.6 months; range, 0-343 months), 46.7% of the eyes developed new or larger chorioretinal spots and 32.6% developed new or recurrent choroidal neovascularization. The 60-month choroidal neovascularization event-free survival was 68.1% (95% confidence interval, 39.2-85.4%). CONCLUSION:: Patients with multifocal choroiditis lesions, but with minimal or no anterior uveitis or vitritis, tended to be young women. Approximately half of the patients presented with bilateral involvement, which is less than has been reported in most case series of multifocal choroiditis with panuveitis. One quarter of all unilaterally affected patients will develop bilateral involvement by 60 months.

IMPORTANCE: With the advent of more sophisticated imaging systems, such as spectral domain optical coherence tomography (SD-OCT), disruption of the inner segment/outer segment (IS/OS) band, and thinning of the outer nuclear layer (ONL) have been identified in association with acute macular neuroretinopathy (AMN). OBJECTIVES: To characterize a new SD-OCT presentation of AMN as a paracentral acute middle maculopathy and to describe multimodal imaging findings that implicate an underlying pathogenesis related to retinal capillary ischemia. DESIGN, SETTING, AND PARTICIPANTS: Retrospective observational case series (January 1, 2012, to January 1, 2013) reviewing clinical and imaging data from 9 patients (11 eyes) with AMN at 6 tertiary referral centers. Lesions were classified as type 1 or 2 in relation to the SD-OCT location of the lesion above (type 1) or below (type 2) the outer plexiform layer (OPL) at 6 tertiary referral centers. RESULTS: Of the 9 patients, 5 were female and 4 were male (mean age, 47.6 years; range, 21-65 years). All patients presented with an acute paracentral scotoma and demonstrated a classic dark gray paracentral lesion with near-infrared imaging. Visual acuity ranged from 20/15 to 20/30. Six eyes (5 patients) had type 1 SD-OCT lesions, also referred to as paracentral acute middle maculopathy, and 5 eyes (4 patients) had type 2 SD-OCT lesions. Although type 1 lesions lead to inner nuclear layer (INL) thinning, type 2 lesions resulted in ONL thinning. Type 2 lesions were always associated with significant outer macular defects, including disruption of the inner segment/outer segment and outer segment/retinal pigment epithelium bands, whereas type 1 lesions spared the outer macula. CONCLUSIONS AND RELEVANCE: Paracentral acute middle maculopathy may represent a novel variant of AMN that affects the middle layers of the macula above the OPL as diagnosed with SD-OCT imaging. Two types of AMN lesions may be seen with SD-OCT occurring above and below the OPL. Type 1 refers to hyperreflective bands in the OPL/INL region with subsequent INL thinning. Type 2 is hyperreflective bands in the OPL/ONL region with subsequent ONL thinning. Type 2 lesions may be associated with concomitant defects of the inner segment/outer segment layer. We propose that each of these lesions may be explained by occlusion of either the superficial capillary plexus (type 1) or deep capillary plexus (type 2) located in the innermost and outermost portion of the INL, respectively, immediately adjacent to each corresponding lesion type.

PURPOSE: To describe a series of previously normotensive eyes experiencing sustained elevated intraocular pressure (IOP) associated with long-term intravitreal antivascular endothelial growth factor (VEGF) therapy for neovascular age-related macular degeneration (AMD). PATIENTS AND METHODS: Clinical data were reviewed for 25 eyes of 23 patients with neovascular AMD who had increased IOP while receiving interval doses of intravitreal ranibizumab and/or bevacizumab. All eyes had tolerated multiple anti-VEGF injections in the past without IOP elevations. RESULTS: After a mean of 20.0 anti-VEGF injections (range, 8-40 injections), the mean IOP was 29.8 mm Hg (range, 22-58 mm Hg), compared with a baseline of 16.9 mm Hg (range, 14-21 mm Hg). The mean highest IOP while receiving intravitreal anti-VEGF therapy was 35.8 mm Hg (range, 23-58 mm Hg). Overall, 23 of 25 cases required IOP management. In the remaining 2 cases, anti-VEGF dosing was switched from regular interval dosing to an optical coherence tomography-guided variable regimen, with subsequent improvement in IOP without antiglaucoma treatment. CONCLUSIONS: Serial injections of anti-VEGF agents may lead to persistent IOP elevations that require glaucoma therapy. The clinician should recognize this phenomenon, as it can occur even if the patient has tolerated multiple prior injections without IOP elevation. Further exploration of the relationship between anti-VEGF therapy and IOP is needed

BACKGROUND: Most patients with central serous chorioretinopathy (CSC) have spontaneous resolution of exudative macular detachments and a good visual prognosis. Patients with CSC have a primary choroidal hyperpermeability problem evident as multifocal areas of hyperpermeability during indocyanine green (ICG) angiography. A small percentage of patients develop chronic or progressive disease with widespread decompensation of the retinal pigment epithelium and severe vision loss. There is no known treatment for this variant of the disorder. PURPOSE: To study ICG-guided photodynamic therapy (PDT) with verteporfin as a potential treatment for patients with chronic CSC. METHODS: Twenty eyes of 15 patients were studied with fluorescein angiography, optical coherence tomography, and ICG angiography to diagnose the maculopathy, monitor the detachments, and localize the choroidal hyperpermeability of the disorder. PDT with ICG guidance was applied to areas of choroidal hyperpermeability, and the patients were observed to determine the anatomic and functional outcomes. RESULTS: Photodynamic therapy guided by ICG was associated with complete resolution of exudative macular detachments in 12 patients and incomplete resolution in the remaining eight eyes. The vision improved in six eyes and remained unchanged in 14 eyes during a mean follow-up of 6.8 months. Six weeks after treatment, the mean visual acuity improved by 0.55 lines, an amount that was marginally significant. There was a significant inverse correlation between the baseline visual acuity and the amount of improvement in acuity at 6 weeks. No patient had any treatment-related side effects. CONCLUSIONS: Indocyanine green angiography-guided PDT with verteporfin seems to aid in the resolution of exudative detachments in patients with chronic CSC. This treatment was associated with a rapid reduction in subretinal fluid and improvement in visual acuity. Although the follow-up time and number of patients in this pilot study were limited, the encouraging results and lack of complications suggest that further study is indicated.

PURPOSE:: To report three cases of solitary, focal retinal phlebitis. METHODS:: An observational case series. RESULTS:: Three eyes in three patients were noted to have unilateral decreased vision, macular edema, and a focal retinal phlebitis, which was not at an arteriovenous crossing. All three patients developed a branch retinal vein occlusion at the site of inflammation. These patients had no other evidence of intraocular inflammation, including vitritis, retinitis, retinal vasculitis, or choroiditis, nor was there any systemic disorder associated with inflammation, infection, or coagulation identified. CONCLUSION:: Focal retinal phlebitis appears to be an uncommon and unique entity that produces macular edema and ultimately branch retinal vein occlusion. In our patients, the focal phlebitis and venous occlusion did not occur at an arteriovenous crossing, which is the typical site for branch retinal venous occlusive disease. This suggests that our cases represent a distinct clinical entity, which starts with a focal abnormality in the wall of a retinal venule, resulting in surrounding exudation and, ultimately, ends with branch retinal vein occlusion

BACKGROUND: Best disease is an autosomal dominant retinal dystrophy with a variable phenotypic expression. Clinically, it is characterized by a vitelliform lesion in the macula because of the deposition of yellow material in a dome-shaped configuration, believed to be lipofuscin that accumulates within and beneath the retinal pigment epithelium. Best disease is occasionally complicated by the development of choroidal neovascularization (CNV), which typically occurs in the macula. We report a case of peripapillary CNV in Best disease. METHODS: Interventional case report. RESULTS: A 12-year-old boy who was previously diagnosed with Best disease was treated with reduced fluence photodynamic therapy for subfoveal CNV in the right eye. After 2 months, he presented with peripapillary CNV in the left eye, which was treated with repeated sessions of reduced fluence photodynamic therapy. CONCLUSION: Ophthalmologists must be aware that peripapillary CNV may occasionally complicate Best disease and can be successfully treated with photodynamic therapy.

PURPOSE: To evaluate long-term effectiveness and safety of intravitreal injection of ranibizumab as a potential treatment for decreased visual acuity secondary to central retinal vein occlusion. METHODS: In this prospective interventional case series, patients with central retinal vein occlusion were administered intravitreal ranibizumab 0.5 mg at baseline and monthly for 2 additional doses. Thereafter, the patients were given additional ranibizumab if they had macular edema by optical coherence tomography, leakage during fluorescein angiography, or any intraretinal hemorrhage. RESULTS: There were 35 eyes of 35 patients who at baseline had a mean visual acuity of 44.2 Early Treatment Diabetic Retinopathy Study letters and a mean central macular thickness of 638 mum. At 12 months, mean visual acuity of 32 eyes improved by 16.5 letters and macular thickness decreased to 164 mum (P < 0.001 vs. baseline for each). At 24 months, mean visual acuity of 24 eyes improved by 17.8 letters and macular thickness was 263 mum (P < 0.001 vs. baseline for each). Patients received an average of 10.2 injections during the first year and 6.6 injections during the second year. No cases of endophthalmitis, retinal detachment, or neovascularization were observed. CONCLUSION: Intravitreal ranibizumab caused a significant improvement in visual acuity and central retinal thickness, which persisted for up to 2 years with minimal side effects

PURPOSE: To compare the spectral-domain optical coherence tomography (SD-OCT) findings of the acute lesions of multifocal choroiditis (MFC) with those of new-onset myopic choroidal neovascularization (CNV). METHODS: Observational case series. A retrospective review comparing the SD-OCT findings of the acute lesions of MFC with those of early myopic CNV. Spectral-domain optical coherence tomography findings in two female patients and one male patient presenting with acute inflammatory lesions of MFC were compared with those of new-onset CNV in three patients with myopic macular degeneration. Each patient underwent a comprehensive eye examination, fundus photography, and fluorescein angiography on the initial visit. The patients underwent SD-OCT scanning at baseline and at follow-up visits using image registration and eye tracking. RESULTS: Spectral-domain optical coherence tomography imaging of the acute lesions of MFC showed drusenlike material between the retinal pigment epithelium and the Bruch membrane, presumed vitreous cells, and localized choroidal hyperreflectivity below the subretinal pigment epithelial material. These SD-OCT findings were not usually present in the eyes with myopic CNV. The subretinal pigment epithelial material corresponded to acute lesions found on color photographs and fluorescein angiography. The subretinal pigment epithelial material and choroidal hyperreflectivity appeared to improve after treatment with antiinflammatory or anti-vascular endothelial growth factor therapy. In contrast, SD-OCT in the patients with myopic CNV showed a very thin choroid, a posterior staphyloma, and a Type 2 (subretinal) neovascular pattern. CONCLUSION: The acute lesions of MFC can be difficult to distinguish from myopic CNV based on clinical examination and fluorescein angiography. However, the inflammatory lesions of MFC can demonstrate characteristic SD-OCT findings not seen with myopic CNV. These SD-OCT findings may help to differentiate these two entities that typically require different treatments

PURPOSE:: The purpose of this study was to report long-term results of intravitreal antivascular endothelial growth factor therapy in the management of choroidal neovascularization in patients with angioid streaks associated with pseudoxanthoma elasticum. METHODS:: A consecutive series of patients with pseudoxanthoma elasticum and choroidal neovascularization were managed with intravitreal antivascular endothelial growth factor injections (bevacizumab 1.25 mg/0.05 mL or ranibizumab 0.5 mg/0.05 mL). The main outcome measures were visual acuity and greatest lesion height as measured by optical coherence tomography. RESULTS:: Nine eyes of nine consecutive patients received intravitreal antivascular endothelial growth factor therapy. During the mean follow-up period of 28.6 months, eyes received an average of 8.4 injections. At baseline, the mean visual acuity was 20/368 (median, 20/60) and improved to 20/281 (median, 20/40) at the last visit (P = 0.14). Visual acuity either improved or stabilized in all 9 eyes (100%). Serial optical coherence tomography measurements showed a mean of 353 mum at baseline and decreased to 146 mum at the last visit (P = 0.005). No complications were noted. CONCLUSION:: These long-term results support the use of intravitreal antivascular endothelial growth factor therapy for the management of choroidal neovascularization in patients with pseudoxanthoma elasticum. Continued experience with intravitreal bevacizumab or ranibizumab in this population will help establish long-term efficacy and better define optimal dosing strategies