CENTRAL RETINAL VEIN OCCLUSION ASSOCIATED WITH USE OF AMYL NITRITE "POPPERS".

PURPOSE: To report a case of central retinal vein occlusion in a young patient after the use of amyl nitrate "poppers." METHODS: Description of the patient's clinical history, ophthalmic examination, retinal imaging, and treatment. RESULTS: A 38-year-old man presented with a central retinal vein occlusion in his right eye after inhaling amyl nitrite "poppers." There appeared to be a definitive temporal association between poppers use and both the onset of the vein occlusion and the patient's visual scotomata, which recurred immediately after drug use multiple times. Optical coherence tomography displayed cystic macular edema, which was treated with intravitreal bevacizumab. The patient's hypercoagulable laboratory workup was negative. CONCLUSION: This is the first report of a central retinal vein occlusion associated with poppers inhalation. A high index of suspicion for poppers use should be maintained in young patients who present with retinal vein occlusion, particularly in homosexual patients with a normal laboratory workup that fails to reveal a hypercoagulable etiology.

Pegcetacoplan for the treatment of geographic atrophy secondary to age-related macular degeneration (OAKS and DERBY): two multicentre, randomised, double-masked, sham-controlled, phase 3 trials.

BACKGROUND: Geographic atrophy is a leading cause of progressive, irreversible vision loss. The objectives of OAKS and DERBY were to assess the efficacy and safety of pegcetacoplan compared with sham treatment in patients with geographic atrophy. METHODS: OAKS and DERBY were two 24-month, multicentre, randomised, double-masked, sham-controlled, phase 3 studies, in which patients aged 60 years and older with geographic atrophy secondary to age-related macular degeneration were enrolled at 110 clinical sites and 122 clinical sites worldwide, respectively. Patients were randomly assigned (2:2:1:1) by central web-based randomisation system to intravitreal 15 mg per 0·1 mL pegcetacoplan monthly or every other month, or sham monthly or every other month using stratified permuted block randomisation (stratified by geographic atrophy lesion area at screening, history or presence of active choroidal neovascularisation in the eye not under assessment, and block size of six). Study site staff, patients, reading centre personnel, evaluating physicians, and the funder were masked to group assignment. Sham groups were pooled for the analyses. The primary endpoint was the change from baseline to month 12 in the total area of geographic atrophy lesions in the study eye based on fundus autofluorescence imaging, in the modified intention-to-treat population (ie, all patients who received one or more injections of pegcetacoplan or sham and had a baseline and at least one post-baseline value of lesion area). Key secondary endpoints (measured at 24 months) were change in monocular maximum reading speed of the study eye, change from baseline in mean functional reading independence index score, change from baseline in normal luminance best-corrected visual acuity score, and change from baseline in the mean threshold sensitivity of all points in the study eye by mesopic microperimetry (OAKS only). Safety analyses included patients who were randomly assigned and received at least one injection of pegcetacoplan or sham. The now completed studies are registered with ClinicalTrials.gov, NCT03525613 (OAKS) and NCT03525600 (DERBY). FINDINGS: Between Aug 30, 2018, and July 3, 2020, 1258 patients were enrolled in OAKS and DERBY. The modified intention-to-treat populations comprised 614 (96%) of 637 patients in OAKS (202 receiving pegcetacoplan monthly, 205 pegcetacoplan every other month, and 207 sham) and 597 (96%) of 621 patients in DERBY (201 receiving pegcetacoplan monthly, 201 pegcetacoplan every other month, and 195 sham). In OAKS, pegcetacoplan monthly and pegcetacoplan every other month significantly slowed geographic atrophy lesion growth by 21% (absolute difference in least-squares mean -0·41 mm2, 95% CI -0·64 to -0·18; p=0·0004) and 16% (-0·32 mm2, -0·54 to -0·09; p=0·0055), respectively, compared with sham at 12 months. In DERBY, pegcetacoplan monthly and pegcetacoplan every other month slowed geographic atrophy lesion growth, although it did not reach significance, by 12% (-0·23 mm2, -0·47 to 0·01; p=0·062) and 11% (-0·21 mm2, -0·44 to 0·03; p=0·085), respectively, compared with sham at 12 months. At 24 months, pegcetacoplan monthly and pegcetacoplan every other month slowed geographic atrophy lesion growth by 22% (-0·90 mm2, -1·30 to -0·50; p<0·0001) and 18% (-0·74 mm2, -1·13 to -0·36; p=0·0002) in OAKS, and by 19% (-0·75 mm2, -1·15 to -0·34; p=0·0004) and 16% (-0·63 mm2, -1·05 to -0·22; p=0·0030) in DERBY, respectively, compared with sham. There were no differences in key secondary visual function endpoints at 24 months. Serious ocular treatment-emergent adverse events were reported in five (2%) of 213, four (2%) of 212, and one (<1%) of 211 patients in OAKS, and in four (2%) of 206, two (1%) of 208, and two (1%) of 206 patients in DERBY receiving pegcetacoplan monthly, pegcetacoplan every other month, and sham, respectively, at 24 months. New-onset exudative age-related macular degeneration was reported in 24 (11%), 16 (8%), and four (2%) patients in OAKS, and in 27 (13%), 12 (6%), and nine (4%) patients in DERBY receiving pegcetacoplan monthly, pegcetacoplan every other month, and sham, respectively, at 24 months. INTERPRETATION: Pegcetacoplan, the first treatment approved by the US Food and Drug Administration for geographic atrophy, slowed geographic atrophy lesion growth with an acceptable safety profile. FUNDING: Apellis Pharmaceuticals.

Efficacy and safety of avacincaptad pegol in patients with geographic atrophy (GATHER2): 12-month results from a randomised, double-masked, phase 3 trial.

BACKGROUND: Geographic atrophy is an advanced form of dry age-related macular degeneration that can lead to irreversible vision loss and high burden of disease. We aimed to assess efficacy and safety of avacincaptad pegol 2 mg in reducing geographic atrophy lesion growth. METHODS: GATHER2 is a randomised, double-masked, sham-controlled, 24-month, phase 3 trial across 205 retina clinics, research hospitals, and academic institutions globally. To be eligible, patients had to be aged 50 years or older with non-centrepoint-involving geographic atrophy and best corrected visual acuity between 20/25 and 20/320 in the study eye. Eligible patients were randomly assigned (1:1) to monthly avacincaptad pegol 2 mg administered as a 100 µL intravitreal injection or sham for the first 12 months. Randomisation was performed using an interactive response technology system with stratification by factors known to be of prognostic importance in age-related macular degeneration. Patients, investigators, study centre staff, sponsor personnel, and data analysts were masked to treatment allocation. The primary endpoint was geographic atrophy lesion size measured by fundus autofluorescence at baseline, month 6, and month 12. Efficacy and safety analyses were done in the modified intention-to-treat and safety populations, respectively. This trial is registered with ClinicalTrials.gov, NCT04435366. FINDINGS: Between June 22, 2020, and July 23, 2021, 1422 patients were screened for eligibility, of whom 448 were enrolled and randomly assigned to avacincaptad pegol 2 mg (n=225) or sham (n=223). One patient in the sham group did not receive study treatment and was excluded from analyses. There were 154 (68%) female patients and 71 (32%) male patients in the avacincaptad pegol 2 mg group, and 156 (70%) female patients and 66 (30%) male patients in the sham group. From baseline to month 12, the mean rate of square-root-transformed geographic atrophy area growth was 0·336 mm/year (SE 0·032) with avacincaptad pegol 2 mg and 0·392 mm/year (0·033) with sham, a difference in growth of 0·056 mm/year (95% CI 0·016-0·096; p=0·0064), representing a 14% difference between the avacincaptad pegol 2 mg group and the sham group. Ocular treatment-emergent adverse events in the study eye occurred in 110 (49%) patients in the avacincaptad pegol 2 mg group and 83 (37%) in the sham group. There were no endophthalmitis, intraocular inflammation, or ischaemic optic neuropathy events over 12 months. To month 12, macular neovascularisation in the study eye occurred in 15 (7%) patients in the avacincaptad pegol 2 mg group and nine (4%) in the sham group, with exudative macular neovascularisation occurring in 11 (5%) in the avacincaptad pegol 2 mg group and seven (3%) in the sham group. INTERPRETATION: Monthly avacincaptad pegol 2 mg was well tolerated and showed significantly slower geographic atrophy growth over 12 months than sham treatment, suggesting that avacincaptad pegol might slow disease progression and potentially change the trajectory of disease for patients with geographic atrophy. FUNDING: Iveric Bio, An Astellas Company.

Avacincaptad pegol for geographic atrophy secondary to age-related macular degeneration: 18-month findings from the GATHER1 trial.

BACKGROUND/OBJECTIVES: To assess the safety and efficacy of avacincaptad pegol (ACP), a C5 inhibitor, for geographic atrophy (GA) secondary to age-related macular degeneration (AMD) over an 18-month treatment course. SUBJECTS/METHODS: This study was an international, prospective, randomized, double-masked, sham-controlled, phase 2/3 clinical trial that consisted of 2 parts. In part 1, 77 participants were randomized 1:1:1 to receive monthly intravitreal injections of ACP 1 mg, ACP 2 mg, or sham. In part 2, 209 participants were randomized 1:2:2 to receive monthly ACP 2 mg, ACP 4 mg, or sham. The mean rate of change of GA over 18 months was measured by fundus autofluorescence. RESULTS: Compared with their respective sham cohorts, monthly ACP treatment reduced the mean GA growth (square root transformation) over 18 months by 28.1% (0.168 mm, 95% CI [0.066, 0.271]) for the 2 mg cohort and 30.0% (0.167 mm, 95% CI [0.062, 0.273]) for the 4 mg cohort. ACP treatment was generally well tolerated over 18 months, with most ocular adverse events (AEs) related to the injection procedure. Macular neovascularization (MNV) was more frequent in both 2 mg (11.9%) and 4 mg (15.7%) cohorts than their respective sham control groups (2.7% and 2.4%). CONCLUSIONS: Over this 18-month study, ACP 2 mg and 4 mg showed continued reductions in the progression of GA growth compared to sham and continued to be generally well tolerated. A pivotal phase 3 GATHER2 trial is currently underway to support the efficacy and safety of ACP as a potential treatment for GA.

HIGH-RESOLUTION SPECTRAL-DOMAIN OPTICAL COHERENCE TOMOGRAPHY OF MULTIPLE EVANESCENT WHITE DOT SYNDROME.

PURPOSE: To evaluate a patient with multiple evanescent white dot syndrome with multimodal imaging including high-resolution spectral-domain optical coherence tomography. METHODS: The patient was evaluated with wide-field color and autofluorescence imaging, microperimetry, and near-infrared imaging. Spectral-domain optical coherence tomography was performed using an instrument capable of 3- µ m axial resolution, the high-resolution Heidelberg Spectralis. RESULTS: A 28-year-old woman developed photopsias and a scotoma in the field of vision of her left eye. She had multiple whitish spots with granularity in her fovea, consistent with the diagnosis of multiple evanescent white dot syndrome. She had supportive fluorescein angiographic and autofluorescence findings. Because of the high resolution and good layer contrast, it was possible to create en face slab images of the external limiting membrane, ellipsoid zone, interdigitation zone, and retinal pigment epithelium. The external limiting membrane showed no abnormalities. There were multiple regions of decreased reflectance in the ellipsoid zone slab but even more prominent changes in the interdigitation zone. The retinal pigment epithelium showed nearly no variation in layer reflectivity. With resolution of symptoms, the color and autofluorescence images returned to normal, the defects in the ellipsoid zone almost completely resolved, and the interdigitation zone continued to show abnormalities. CONCLUSION: Although past studies concluded that the ellipsoid zone was the main region of involvement in multiple evanescent white dot syndrome, high-resolution spectral-domain optical coherence tomography suggests the interdigitation zone was more prominently affected in this case.

Efficacy and safety of brolucizumab versus aflibercept in eyes with early persistent retinal fluid: 96-week outcomes from the HAWK and HARRIER studies.

OBJECTIVE: Post-hoc analysis to compare the outcomes of brolucizumab 6 mg vs. aflibercept 2 mg in neovascular age-related macular degeneration (nAMD) patients with early persistent retinal fluid in HAWK and HARRIER. METHODS: After 3 monthly loading doses, brolucizumab-treated eyes (N = 730) received injections every 12 weeks (q12w) or q8w if disease activity was detected. Aflibercept-treated eyes (N = 729) received fixed q8w dosing. Early persistent fluid was defined as the presence of subretinal fluid and/or intraretinal fluid up to Week 12. RESULTS: A lower proportion of brolucizumab patients had early persistent retinal fluid compared with aflibercept (11.2% (n = 82) vs. 19.2% (n = 140)). In these patients, 34.1% of the brolucizumab-treated group achieved a ≥ 15 ETDRS letter gain in best corrected visual acuity (BCVA) from baseline at Week 96 compared with 20.7% of the aflibercept-treated group. Brolucizumab achieved numerically better BCVA outcomes (Week 96: brolucizumab, +6.4 letters; aflibercept, +3.7 letters) and significantly greater central subfield thickness reductions versus aflibercept from baseline through Week 96 (Week 96: -202 µm vs. -145 µm; p = 0.0206). Brolucizumab demonstrated an overall favourable benefit/risk profile in this patient cohort. In their unmasked, post-hoc review, the Safety Review Committee identified two cases of retinal vasculitis and no cases of retinal vascular occlusion in the brolucizumab arm; no cases of retinal vasculitis or retinal vascular occlusion were identified in the aflibercept arm. CONCLUSION: In this analysis, anatomical and visual outcomes were better with brolucizumab compared with aflibercept. Brolucizumab may therefore achieve greater disease control than aflibercept in nAMD patients with early persistent retinal fluid.

Evaluation of a self-imaging SD-OCT system designed for remote home monitoring.

PURPOSE: To compare identification rates of retinal fluid of the Notal Vision Home Optical Coherence Tomography (OCT) device (NVHO) when used by people with age-related macular degeneration (AMD) to those captured by a commercial OCT. METHODS: Prospective, cross-sectional study where patients underwent commercial OCT imaging followed by self-imaging with either the NVHO 2.5 or the NVHO 3 in clinic setting. Outcomes included patients' ability to acquire analyzable OCT images with the NVHO and to compare those with commercial images. RESULTS: Successful images were acquired with the NVHO 2.5 in 469/531 eyes (88%) in 264/290 subjects (91%) with the mean (SD) age of 78.8 (8.8); 153 (58%) were female with median visual acuity (VA) of 20/40. In the NVHO 3 cohort, 69 eyes of 45 subjects (93%) completed the self-imaging. Higher rates of successful imaging were found in eyes with VA ≥ 20/320. Positive percent agreement/negative percent agreement for detecting the presence of subretinal and/or intraretinal fluid when reviewing for fluid in three repeated volume scans were 97%/95%, respectively for the NVHO v3. CONCLUSION: Self-testing with the NVHO can produce high quality images suitable for fluid identification by human graders, suggesting the device may be able to complement standard-of-care clinical assessments and treatments.

Subretinal Fluid Resolution and Visual Acuity in Patients with Neovascular Age-Related Macular Degeneration: A HARBOR Post Hoc Analysis.

OBJECTIVE: To determine the effect of subretinal fluid (SRF) resolution on visual acuity in patients with neovascular age-related macular degeneration (nAMD) from the HARBOR trial. DESIGN: Post hoc analysis of the HARBOR trial (a phase 3, double-masked, randomized, active treatment-controlled trial of ranibizumab conducted between July 2009 and August 2012 [NCT00891735]) was carried out from January 2020 to July 2021. PARTICIPANTS: Treatment-naive patients with nAMD and active subfoveal choroidal neovascularization (N = 1097). Multiple intervention arms were pooled for this analysis if SRF was present at baseline and intraretinal fluid/SRF resolved during the study, based on spectral-domain OCT (n = 349). INTERVENTION: Three monthly loading doses followed by intravitreal injections of 0.5-mg or 2.0-mg ranibizumab were administered monthly or pro re nata over 24 months. MAIN OUTCOME MEASURES: Mean change in ETDRS best-corrected visual acuity (BCVA) between the month before SRF resolution and the month of SRF resolution detection. Visual outcomes at months 12 and 24 were analyzed in eyes without SRF recurrence after SRF resolution. The proportion of patients who lost ≤ 4 letters were considered as vision gainers/maintainers and those who lost ≥ 5 were considered as vision losers. RESULTS: Of 349 patients, 32 patients (9%) lost ≥ 5 ETDRS letters (mean [95% confidence interval (CI)], -9.9 letters [-12.0, -7.9]) and 317 (91%) of the eyes gained/maintained BCVA (mean, 6.1 letters [95% CI, 5.3, 6.8]) between the month before SRF resolution and the month of SRF resolution. There were no differences in baseline ocular characteristics between patient groups. Among eyes without SRF recurrence after SRF resolution (64%; 224/349), eyes that lost ≥ 5 ETDRS letters compared with those that gained/maintained letters at the time of SRF resolution had reduced visual outcome gains from baseline to month 12 (1.4 vs. 12.9 letters) and month 24 (0.0 vs. 12.6 letters). CONCLUSIONS: A greater proportion of ranibizumab-treated eyes with nAMD gained/maintained visual acuity at SRF resolution. Approximately 9% of eyes lost vision during SRF resolution; these eyes had reduced final visual acuity gains at 12 and 24 months. Further analyses are warranted to investigate potential underlying factors and discuss the treatment implications if confirmed.

Early Experience With Brolucizumab Treatment of Neovascular Age-Related Macular Degeneration.

IMPORTANCE: Outcome data are limited regarding early experience with brolucizumab, the most recently approved anti-vascular endothelial growth factor (VEGF) agent for the treatment of neovascular age-related macular degeneration (nAMD). OBJECTIVE: To report clinical outcomes after intravitreous injection (IVI) of brolucizumab, 6 mg, for nAMD. DESIGN, SETTING, AND PARTICIPANTS: This retrospective case series conducted at 15 private or academic ophthalmological centers in the United States included all consecutive patients with eyes treated with brolucizumab by 6 retina specialists between October 17, 2019, and April 1, 2020. EXPOSURES: Treatment with brolucizumab IVI, 6 mg. MAIN OUTCOMES AND MEASURES: Change in mean visual acuity (VA) and optical coherence tomography parameters, including mean central subfield thickness and presence or absence of subretinal and/or intraretinal fluid. Secondary outcomes included ocular and systemic safety. RESULTS: A total of 172 eyes from 152 patients (87 women [57.2%]; mean [SD] age, 80.0 [8.0] years) were included. Most eyes (166 [96.5%]) were not treatment naive, and 65.7% of these eyes (109 of 166) were switched from the prior anti-VEGF agent because of persistent fluid detected on optical coherence tomography scans. Study eyes received a mean (SD) of 1.46 (0.62) brolucizumab IVIs. The mean (SD) VA prior to starting brolucizumab was a 64.1 (15.9) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score (Snellen equivalent, 20/50) and was a 63.3 (17.2) ETDRS letter score (Snellen equivalent, 20/63) at the last study evaluation (mean difference, 0.8; 95% CI, -2.7 to 4.3; P = .65). When analyzed by number of brolucizumab IVIs, the presence or absence of fluid prior to starting brolucizumab, or the presence or absence of intraocular inflammation after receiving brolucizumab, there was no difference in mean VA prior to starting brolucizumab compared with after brolucizumab IVIs or at the final study evaluation. The mean (SD) central subfield thickness in all eyes prior to starting brolucizumab was 296.7 (88.0) µm and was 269.8 (66.5) µm at the last study examination (mean difference, 26.9 µm; 95% CI, 9.0-44.7 µm; P = .003). Intraocular inflammation was reported in 14 eyes (8.1%) and was self-limited and resolved without treatment in almost half those eyes (n = 6). One previously reported eye (0.6%) had occlusive retinal vasculitis and severe loss of vision. CONCLUSIONS AND RELEVANCE: In this analysis of brolucizumab IVI for nAMD, VA remained stable, with a reduction in central subfield thickness. Intraocular inflammation events ranged from mild with spontaneous resolution to severe occlusive retinal vasculitis in 1 eye.

Choroidal Melanoma Simulating Adenoma of the Retinal Pigment Epithelium Arising at the Site of Congenital Hypertrophy of the Retinal Pigment Epithelium.

Neoplasms of the retinal pigment epithelium (RPE) are rare tumors that can simulate choroidal melanoma, but clinical and imaging characteristics often differentiate these lesions. We report a 70-year-old male with an abruptly elevated pigmented lesion that arose at the site of congenital hypertrophy of the RPE and demonstrated associated exudation, as well as feeding and draining vessels, suggestive of RPE adenoma. Optical coherence tomography showed retinal elevation with serous retinal detachment adjacent to the mass, and ultrasonography revealed an abruptly elevated, moderately echodense mass of 6.4-mm thickness. Fluorescein -angiography showed early tumor hypofluorescence, late -tumor hyperfluorescence with staining and leakage, and -retinal vessels buried under the mass, suggestive of a retinal tumor. The patient was monitored with the presumed diagnosis of RPE adenoma, but 3 months later, the growth was documented and fine-needle aspiration biopsy revealed choroidal melanoma. Management with I-125 plaque radiotherapy was performed leading to tumor regression and a thickness of 4.6 mm.

CLOSURE OF SMALL MACULAR HOLES USING VITRECTOMY SURGERY WITH INTERNAL LIMITING MEMBRANE PEELING WITHOUT THE USE OF INTRAOCULAR GAS TAMPONADE: BROADENING THE UNDERSTANDING OF THE MACULAR HOLE PATHOPHYSIOLOGY.

PURPOSE: To determine whether small macular hole closure can be achieved with 25-G vitrectomy surgery with internal limiting membrane peeling without the use of intraocular gas tamponade or facedown positioning. METHODS: 25-G vitrectomy surgery with internal limiting membrane peeling without the use of intraocular gas tamponade or positioning was performed on 20 eyes with a small (<400-µm diameter), full-thickness macular hole. RESULTS: In 17 of 20 eyes (85%), the hole had closed. Three holes had closed by Postoperative Day 1, 13 holes by Postoperative Week 1, 16 holes by Postoperative Week 2, and 17 holes by Postoperative Week 6. At Postoperative Month 1, vision improved in 16 of 17 eyes in which the macular hole had closed. One hole that had not closed at the first postoperative week and two holes that had not closed at the third postoperative week required follow-up surgery with intraocular gas tamponade and facedown positioning, after which the hole closed. The mean preoperative visual acuity was 0.626 logMAR (20/85), and the mean postoperative visual acuity after 1 month was 0.392 logMAR (20/50) (P < 0.001). CONCLUSION: Vitrectomy surgery with internal limiting membrane peeling without the use of gas tamponade or positioning can achieve closure of small macular holes.

Expanded spectral domain-OCT findings in the early detection of hydroxychloroquine retinopathy and changes following drug cessation.

PURPOSE: To report expanded SD-OCT findings of HCQ retinopathy that may assist the clinician in earlier diagnosis. To characterize structural changes of HCQ retinopathy with SD-OCT after drug cessation. METHODS: Setting: Private practice and academic institution. Patient Population: Patients at New England Eye Center and Ophthalmic Consultants of Boston in Boston, MA diagnosed with HCQ retinopathy and followed after drug cessation. Retrospective clinical data review by the Boston Image Reading Center. Main Outcome Measures: SD-OCT findings suggestive of HCQ retinopathy before parafoveal ellipsoid disruption. Change in SD-OCT morphological appearance and retinal thickness of each of the nine subfields corresponding to the Early Treatment of Diabetic Retinopathy Study areas. RESULTS: Thirty eyes with HCQ retinopathy were followed with SD-OCT after drug cessation. Findings before disruption of the parafoveal EZ included parafoveal outer nuclear layer (ONL) thinning, disruption of the parafoveal interdigitation zone, and reduced reflectivity of the parafoveal EZ. In early toxicity, 75 % developed progression after drug cessation, including disruption of the parafoveal EZ and retinal pigment epithelium and thinning of the ONL. Eyes with obvious toxicity had greater inferior outer ring thinning 12 months after drug cessation compared to early toxicity (p = 0.002, 95 % CI -2 to -8 µm). In obvious toxicity, the nasal inner subfield showed more thinning than the temporal inner subfield at 12 months after drug cessation (p = 0.018, 95 % CI -1 to -8 µm). CONCLUSIONS: Once HCQ retinopathy is diagnosed and the medication is discontinued, structural retinal changes commonly occur.

Vascular endothelial growth factor and diabetic macular edema.

Diabetes mellitus is a major global health epidemic, and diabetic macular edema is the leading cause of vision loss in this population. Macular focal and/or grid laser photocoagulation applied to microaneurysms and thickened retina had long been primary therapy for diabetic macular edema. Chronically elevated serum glucose is known to cause breakdown in the inner and outer retinal blood barrier resulting in upregulation of vascular endothelial growth factor (VEGF). Intravitreal anti-vascular endothelial growth factor agents, including ranibizumab, bevacizumab, and aflibercept, have been shown in randomized clinical trials to be superior to macular laser for the treatment of clinically relevant diabetic macular edema. The READ-2, RISE/RIDE, and RESTORE trials established ranibizumab's superiority to macular laser, whereas the BOLT trial demonstrated bevacizumab's superiority to laser. The DRCR.net Protocol T results showed that intravitreal aflibercept, bevacizumab, and ranibizumab were all effective in reducing retinal thickness secondary to diabetic edema and in improving vision. When the presenting vision was 20/40 or better, visual improvement was equivalent. With eyes presenting with 20/50 or worse vision, aflibercept was superior with respect to visual improvement. Intravitreal anti-VEGF therapy can be burdensome for the patient and health care system, often requiring monthly treatment visits. To reduce burdens, anti-VEGF strategies are in development to lengthen the treatment interval.

Optical Coherence Tomography Angiography for Detecting Choroidal Neovascularization Secondary to Choroidal Osteoma.

Choroidal osteoma is an ossifying tumor that is found predominantly in the peripapillary and macular areas. It typically affects otherwise healthy females. Vision loss may occur secondary to the development of choroidal neovascularization (CNV). Fluorescein angiography (FA) remains the gold standard for diagnosing CNV; however, the use of optical coherence tomography angiography (OCTA) as an adjunct to FA is growing. In this report, a 16-year-old female with a large, unilateral peripapillary choroidal osteoma presented with blurred vision. Exam revealed scattered intraretinal hemorrhage, but FA was unable to detect CNV overlying the tumor. OCTA detected abnormal flow in the outer retina corresponding to a type 2 CNV. Following intravitreal anti-vascular endothelial growth factor therapy, the CNV regressed, the hemorrhage resolved, and there was less fluid. OCTA may be helpful in detecting CNV noninvasively in eyes in which FA is equivocal, such as those with choroidal osteoma.

A UNIQUE POSTERIOR SEGMENT PHENOTYPIC MANIFESTATION OF COXSACKIE VIRUS INFECTION.

PURPOSE: To report a posterior segment phenotypic manifestation of Coxsackie virus infection that has not been previously appreciated. METHODS: The clinical course and multimodal imaging findings, including spectral domain optical coherence tomography, fluorescein angiography, near infrared reflectance, and fundus autofluorescence of two patients with Coxsackie virus infections were documented. RESULTS: A neurosensory macular detachment was present in both patients on baseline examination. Fluorescein angiography demonstrated pooling within this lesion and spectral domain optical coherence tomography identified thickening of the retinal pigment epithelial band with variable degrees of attenuation of the ellipsoid zone and interdigitation zone. Fundus autofluorescence and near infrared reflectance imaging revealed multiple satellite lesions adjacent to the neurosensory detachment. These lesions were not seen on fluorescein angiography or color photography. Satellite lesions were hyporeflective on near infrared reflectance imaging and hyperautofluorescent on fundus autofluorescence imaging. The satellite lesions correlated with sites of ellipsoid disruption on spectral domain optical coherence tomography. Both patients were observed and their condition improved over the course of time. There was total resolution of satellite lesions, reconstitution of the ellipsoid zone and interdigitation zone, and return of retinal pigment epithelial thickness to the normal range. A bull's eye pattern of macular retinal pigment epithelial disturbance persisted on color and near infrared reflectance images, despite good visual acuity. CONCLUSION: Posterior segment Coxsackie virus infection may concurrently express the clinical characteristics of acute idiopathic maculopathy and multifocal retinitis. The visual prognosis in this variant is usually favorable. The multimodal imaging features that characterize this entity should be recognized to avoid confusion with other diseases that have a similar presentation.

Retinal Pigment Epithelial Adenocarcinoma Presenting as an Amelanotic Mass.

Retinal pigment epithelium (RPE) neoplasms are extraordinarily rare and have been infrequently described in the literature. Most RPE tumors are pigmented and may simulate choroidal melanoma. The best management of RPE tumors has not yet been elucidated. In the current case, a 36-year-old man presenting with visual disturbance is found to have biopsy-proven RPE adenocarcinoma with subfoveal fluid. He is treated with grid laser over the lesion with complete resolution of fluid. RPE adenocarcinoma can present as an amelanotic mass, and grid laser over the lesion may represent a novel approach for treating associated subretinal fluid.

Confirmation of Choroidal Varix Through Divot Sign on Spectral-Domain Optical Coherence Tomography.

Enhanced depth imaging spectral-domain optical coherence tomography (EDI SD-OCT) provides a rapid and easily accessible measure to evaluate suspicious choroidal lesions. A 60-year-old woman was referred for evaluation of an inferotemporal slightly pigmented lesion that showed a large hyporeflective elevation in the deep choroid on EDI SD-OCT. After applying pressure to the globe, repeat EDI SD-OCT showed flattening of the lesion with a prominent depression or "divot" within the choroid of the center of the lesion. If noted on imaging, this divot sign is an additional reproducible diagnostic finding that can correctly identify a suspicious choroidal lesion as a benign choroidal varix.