The 10q26 Risk Haplotype of Age-Related Macular Degeneration Aggravates Subretinal Inflammation by Impairing Monocyte Elimination.

A minor haplotype of the 10q26 locus conveys the strongest genetic risk for age-related macular degeneration (AMD). Here, we examined the mechanisms underlying this susceptibility. We found that monocytes from homozygous carriers of the 10q26 AMD-risk haplotype expressed high amounts of the serine peptidase HTRA1, and HTRA1 located to mononuclear phagocytes (MPs) in eyes of non-carriers with AMD. HTRA1 induced the persistence of monocytes in the subretinal space and exacerbated pathogenic inflammation by hydrolyzing thrombospondin 1 (TSP1), which separated the two CD47-binding sites within TSP1 that are necessary for efficient CD47 activation. This HTRA1-induced inhibition of CD47 signaling induced the expression of pro-inflammatory osteopontin (OPN). OPN expression increased in early monocyte-derived macrophages in 10q26 risk carriers. In models of subretinal inflammation and AMD, OPN deletion or pharmacological inhibition reversed HTRA1-induced pathogenic MP persistence. Our findings argue for the therapeutic potential of CD47 agonists and OPN inhibitors for the treatment of AMD.

Splenic monocytes drive pathogenic subretinal inflammation in age-related macular degeneration.

Age-related macular degeneration (AMD) is invariably associated with the chronic accumulation of activated mononuclear phagocytes in the subretinal space. The mononuclear phagocytes are composed of microglial cells but also of monocyte-derived cells, which promote photoreceptor degeneration and choroidal neovascularization. Infiltrating blood monocytes can originate directly from bone marrow, but also from a splenic reservoir, where bone marrow monocytes develop into angiotensin II receptor (ATR1)+ splenic monocytes. The involvement of splenic monocytes in neurodegenerative diseases such as AMD is not well understood. Using acute inflammatory and well-phenotyped AMD models, we demonstrate that angiotensin II mobilizes ATR1+ splenic monocytes, which we show are defined by a transcriptional signature using single-cell RNA sequencing and differ functionally from bone marrow monocytes. Splenic monocytes participate in the chorio-retinal infiltration and their inhibition by ATR1 antagonist and splenectomy reduces the subretinal mononuclear phagocyte accumulation and pathological choroidal neovascularization formation. In aged AMD-risk ApoE2-expressing mice, a chronic AMD model, ATR1 antagonist and splenectomy also inhibit the chronic retinal inflammation and associated cone degeneration that characterizes these mice. Our observation of elevated levels of plasma angiotensin II in AMD patients, suggests that similar events take place in clinical disease and argue for the therapeutic potential of ATR1 antagonists to inhibit splenic monocytes for the treatment of blinding AMD.

Real-world experience with brolucizumab in neovascular age-related macular degeneration over 2 years: the REBA extension study.

BACKGROUND: To determine long-term efficacy and safety of intravitreal brolucizumab therapy for neovascular age-related macular degeneration (nAMD) in the real-world setting. METHODS: Retrospective, observational, multicentric study and an extension of the REBA study (Real-world Experience with Brolucizumab in nAMD) to 24 months. The study entailed follow-up of 91 consecutive eyes (67 patients) with nAMD who received brolucizumab therapy and completed 24 months of follow-up. Both treatment-naïve and switch therapy patients were included. All relevant data were collected. The primary outcome measure was changed in best-corrected visual acuity (BCVA) over time. Secondary outcome measures included change in central subfield thickness (CST) and complications. RESULTS: The mean (SD) baseline BCVA was 48.4 (3.5) letters and 36.2 (7.1) letters in treatment-naïve group and switch therapy group, respectively. BCVA gain was + 9.2 (3.7) letters (p = 0.01) and + 7.7 (3.4) letters (p = 0.011), respectively. The change in mean (SD) CST has shown a significant decrease in retinal thickness in treatment-naïve group (from 432.5 (68.4) to 283.0 (51.3) µm; p = 0.018) and in switch therapy group (from 452.5 (40.5) to 271.0 (43.4) µm; p = 0.011) group. One switch patient developed vascular occlusion and another a macular hole after the fifth brolucizumab injection as reported in the primary study. Both patients recovered uneventfully. Three patients demonstrated reversible intraocular inflammation between months 10 and 24. CONCLUSION: Patients showed a significant anatomical and functional response to brolucizumab therapy in the real world, regardless of prior treatment status, until the end of the follow-up period. Overall, 5 significant untoward events were noted.

Melanophages give rise to hyperreflective foci in AMD, a disease-progression marker.

Retinal melanosome/melanolipofuscin-containing cells (MCCs), clinically visible as hyperreflective foci (HRF) and a highly predictive imaging biomarker for the progression of age-related macular degeneration (AMD), are widely believed to be migrating retinal pigment epithelial (RPE) cells. Using human donor tissue, we identify the vast majority of MCCs as melanophages, melanosome/melanolipofuscin-laden mononuclear phagocytes (MPs). Using serial block-face scanning electron microscopy, RPE flatmounts, bone marrow transplantation and in vitro experiments, we show how retinal melanophages form by the transfer of melanosomes from the RPE to subretinal MPs when the "don't eat me" signal CD47 is blocked. These melanophages give rise to hyperreflective foci in Cd47-/--mice in vivo, and are associated with RPE dysmorphia similar to intermediate AMD. Finally, we show that Cd47 expression in human RPE declines with age and in AMD, which likely participates in melanophage formation and RPE decline. Boosting CD47 expression in AMD might protect RPE cells and delay AMD progression.

Visual outcomes of macular melanocytic lesions after early or delayed proton beam therapy.

PURPOSE: During their initial management, some macular melanocytic lesions can be closely monitored to wait for a documented growth before advocating a treatment by irradiation. However, the visual outcomes of this strategy have not yet been assessed. This study compares the visual outcomes of macular melanocytic lesions that underwent delayed proton beam therapy (PBT) after an initial observation to those treated early. METHODS: A total of 162 patients with suspicious melanocytic lesions whose margins were located within 3 mm of the fovea were recruited from two French ocular oncology centers. RESULTS: Overall, 82 patients treated with PBT within 4 months after the initial visit (early PBT group) were compared to 24 patients treated with delayed PBT (delayed PBT group) and 56 patients not treated with PBT (observation group). Visual acuity was not significantly different between baseline and last visit in the observation group (p = 0.325). Between baseline and last visit, the median [IQR] loss in visual acuity was significant in both the early (0.7 [0.2; 1.8], p < 0.001) and the delayed (0.5 [0.2; 1.5], p < 0.001) PBT groups. After irradiation, there was no significant difference between the early and delayed PBT groups for visual loss (p = 0.575), diameter reduction (p = 0.190), and thickness lowering (p = 0.892). In multivariate analysis, history of diabetes mellitus and Bruch's membrane rupture remained significantly associated with greater visual loss (p = 0.036 and p = 0.002, respectively). CONCLUSION: For small lesions in which there is no clear diagnosis of malignant melanoma, an initial close monitoring to document tumor growth does not impact visual prognosis, despite the potential complications associated with the untreated tumor. However, the survival should remain the main outcome of the treatment of these lesions.

REAL WORLD STUDY COMPARING PHAKIC VERSUS PSEUDOPHAKIC EYES IN DIABETIC MACULAR EDEMA TREATED WITH DEXAMETHASONE IMPLANT: The PHAKIDEX Study.

PURPOSE: Dexamethasone implant (DEX-implant) is one treatment choice in diabetic macular edema. However, steroid-induced cataract is a common complication when treating a chronic disease and could lead to vision loss. Because of the lack of studies specifically focused on the functional outcomes according to the lens status, the authors therefore aim to analyze the effectiveness and safety of DEX-implant treatment for diabetic macular edema in phakic versus pseudophakic eyes. METHODS: This multicenter, retrospective study conducted in France included eyes of consecutive patients who had received a DEX-implant for diabetic macular edema. RESULTS: A total of 328 eyes were included: 158 eyes (48.2%) were phakic, 167 eyes (50.9%) were pseudophakic and three were unknown. According to the lens status, mean change in best-corrected visual acuity from baseline was never significantly different between phakic and pseudophakic eyes (likelihood ratio test, P = 0.09) nor in the change in central macular thickness (likelihood ratio test, P = 0.79) in multivariate analysis. Cataract surgery was performed in 63 phakic eyes (39.9%) during the study period with a mean delay of 8.1 months (CI95% [6.59-9.69]). The mean change in best-corrected visual acuity between phakic eyes who underwent cataract surgery and those who did not, was not significantly different during the follow-up at each visit. The risk of ocular hypertension was not statistically different between phakic and pseudophakic subsets ( P = 0.9). CONCLUSION: The authors showed here that phakic eyes treated with DEX-implant for diabetic macular edema did not have a significant difference in visual gain in comparison to pseudophakic eyes, with a comparable safety profile.

The Effects of Treatment Regimen on the Initial Management of Macular Neovascularization Subtypes in Age-Related Macular Degeneration.

INTRODUCTION: The aim of this study was to evaluate the effect of initial treatment regimen individualization (pro re nata or treat-and-extend [TAE]), according to macular neovascularization (MNV) subtype, on the functional and anatomical response in neovascular age-related macular degeneration (nAMD). The secondary objective was to compare the treatment burden between each MNV subtype. METHODS: Consecutive treatment-naïve nAMD patients were retrospectively included. MNV subtype was graded by 2 independent blinded investigators on multimodal imaging. Functional and anatomical outcomes were analysed according to treatment regimen and MNV subtypes. RESULTS: A total of 281 eyes from 243 patients were included in the study. According to the treatment regimen, there was no significant difference in best-corrected visual acuity gain within the first 2 years of treatment for type 1 (p = 0.106) and type 3 MNV (p = 0.704). Conversely, there was a significant difference in favour of TAE regimen for type 2 (p = 0.017) and type 4 MNV (p = 0.047). Type 1 MNV had a higher proportion of visits with subretinal fluid (p = 0.0007) but not with intraretinal fluid (p = 0.22). The mean interval between the last 2 injections was significantly shorter for type 1 MNV (p = 0.0045). CONCLUSION: The individualization of the initial treatment protocol according to MNV subtype can improve the functional outcome and may decrease the treatment burden.

Screening of telangiectatic capillaries in chronic macular edema based on multimodal imaging: a study of 101 eyes. LyoMAC1 study.

PURPOSE: To estimate the prevalence of telangiectatic capillaries (TCs) in patients followed for chronic macular edema (CME) (diabetic ME [DME] and ME associated with retinal vein occlusion [RVO]). METHODS: Real-life, prospective, bi-centric cohort study including all consecutive patients followed for a clinically significant CME secondary to diabetic retinopathy or RVO. Inclusion criteria were patients treated with intravitreal injection for their ME for at least 12 months who had to undergo follow-up angiography. Multimodal imaging with color retinophotography, spectral-domain optical coherence tomography (SD-OCT), OCT angiography, and en face OCT was performed in all patients. RESULTS: A total of 101 eyes of 71 patients were included between November 2019 and June 2020. Of the 101 eyes analyzed, indocyanine green angiography found at least one TC in 67 eyes (66.3%). No significant differences were found between the groups with and without TC except for the distribution of DME and RVO (p < 0.008). In 83.6% of eyes with TCs, TCs contributed to the formation of the ME. SD-OCT sensitivity for TC detection was 94%. CONCLUSION: In our study, the estimated prevalence of TCs in CME (DME and ME associated with RVO) was 66.3%, i.e., two-thirds of patients. SD-OCT was an excellent screening examination with a sensitivity of 94%.

CLINICAL FEATURES OF RETINAL METASTASES: New Cases Integrated in a Systematic Review of the Literature.

PURPOSE: To report a cohort of patients diagnosed with retinal metastases (RM), and to integrate these new cases in a systematic review of the literature, analyzing the clinical features and prognosis factors of patients with RM. METHODS: We conducted a retrospective multicenter study including patients with RM. We also performed a full literature review of all published cases with a diagnosis of RM. RESULTS: A total of six new cases were described on multimodal imaging. By combining the data from the literature and from our patients, we report the characteristics of a total of 69 patients. The most frequent primary tumor sites were cutaneous melanoma (36%), lung (23%), gastrointestinal tract (17%), and breast (12%). Multimodal imaging highlighted specific characteristics of RM. Fluorescein and indocyanine green angiography revealed early hypofluorescence followed by progressive filling of intrinsic dilated vessels. Optical coherence tomography demonstrated a hyperreflective intraretinal mass in all cases with or without subretinal fluid, hyperreflective intraretinal dots, or intraretinal fluid. Ultrasonography revealed a medium-high reflective dome-shaped tumor. Fifty-nine percent of the patients died during the follow-up with a mean survival time of 8.8 ± 8.7 months. CONCLUSION: We described here the clinical spectrum of RM and highlighted specific features of the disease.

COMPARISON OF PRIMARY AND SECONDARY FORMS OF MULTIPLE EVANESCENT WHITE DOT SYNDROME.

PURPOSE: The aim of this study was to compare primary versus secondary forms of multiple evanescent white dot syndrome (MEWDS) at T0 (baseline) and T1 (1-4 months after the onset of symptoms). METHODS: A total of 101 eyes in 100 patients were included in a multicentric retrospective study. RESULTS: Secondary MEWDS was defined as MEWDS associated with underlying chorioretinal inflammatory pathologies, mainly multifocal choroiditis and punctuate inner choroidopathy. Patients with secondary MEWDS were older (P = 0.011). The proportion of women (P = 0.8), spherical equivalent (P = 0.3), and best-corrected visual acuity at T0 (P = 0.2) were not significantly different between the two groups. The area of MEWDS lesions on late-phase indocyanine green angiography was significantly smaller in secondary MEWDS (P = 0.001) and less symmetrical with respect to both horizontal (P = 0.003) and vertical (P = 0.004) axis. At T0, neither the clinical (P = 0.5) nor the multimodal imaging (P = 0.2) inflammation scores were significantly different between the groups. At T1, the multimodal imaging inflammation score was higher in secondary MEWDS (P = 0.021). CONCLUSION: In secondary MEWDS, outer retinal lesions are less extensive and located close to preexisting chorioretinal lesions. Mild signs of intraocular inflammation on multimodal imaging are more frequent in secondary MEWDS during recovery. These findings suggest that chorioretinal inflammation may trigger secondary MEWDS.

EFFICACY AND SAFETY OF AFLIBERCEPT FOR THE TREATMENT OF IDIOPATHIC CHOROIDAL NEOVASCULARIZATION IN YOUNG PATIENTS: The INTUITION Study.

PURPOSE: To evaluate the mean change in visual acuity at 52 weeks in patients with idiopathic choroidal neovascularization treated with aflibercept. METHODS: We conducted a prospective noncomparative open-label Phase-II trial. The dosage regimen evaluated in this study was structured into two periods: (1) from inclusion to 20 weeks: a treat-and-extend period composed of three mandatory intravitreal injections, and complementary intravitreal injections performed if needed; (2) from 21 weeks to 52 weeks: a pro re nata period composed of intravitreal injections performed only if needed. RESULTS: A total of 19 patients were included, and 16 completed the 52-week study. At baseline, the mean best corrected visual acuity was 66.56 (±20.72) letters (≈20/50 Snellen equivalent), and the mean central retinal thickness was 376.74 µm (±93.77). At 52 weeks, the mean change in the best-corrected visual acuity was +19.50 (±19.36) letters [95% confidence interval = +9.18 to +29.82]. None of the patients included lost ≥15 letters at 24 weeks or 52 weeks. The mean change in central retinal thickness was -96.78 µm (±104.29) at 24 weeks and -86.22 µm (±112.27) at 52 weeks. The mean number of intravitreal injections was 5.4 (±3.0) at 52-weeks. No ocular serious adverse events related to the treatment were reported. CONCLUSION: The present analysis shows clinically significant functional and anatomical treatment effect of aflibercept in case of idiopathic choroidal neovascularization. The treat-and-extend regimen proposed after the first injection seems adequate to treat most neovessels.

QUANTITATIVE ANALYSIS OF CHORIOCAPILLARIS ALTERATIONS IN SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY-ANGIOGRAPHY DURING RADIATION RETINOPATHY.

PURPOSE: To evaluate choriocapillaris alterations following proton beam therapy irradiation using swept-source optical coherence tomography-angiography, and to assess their correlation with the grade of radiation retinopathy (RR). METHODS: Eyes with uveal melanoma evaluated before and after irradiation with proton beam therapy were included, as well as the healthy fellow eye. The gradation of RR was based on a previously published classification. Choriocapillaris flow voids area was analyzed using Phansalkar thresholding. Retinal vascularization was described by foveal avascular zone (FAZ) perimeter, FAZ area, FAZ circularity index, and percentage of nonperfusion area (PAN) in the superficial capillary plexus (SCP) or deep capillary plexus. RESULTS: A total of 157 eyes of 83 patients were analyzed. Overall, there was a significant difference between the control group, the uveal melanoma before proton beam therapy group, and the grades of RR in the uveal melanoma after proton beam therapy group for FAZ perimeter ( P < 0.001), FAZ area ( P < 0.001), FAZ-circularity index ( P < 0.001), PAN-SCP ( P < 0.001), PAN-deep capillary plexus ( P < 0.001), and choriocapillaris flow voids area ( P < 0.001). Moreover, choriocapillaris flow voids area was significantly increased in the early stages of RR ( P = 0.003) and was further significantly correlated with FAZ perimeter ( P < 0.001), FAZ area ( P < 0.001), FAZ-circularity index ( P = 0.010), PAN-SCP ( P < 0.001), and PAN-deep capillary plexus ( P < 0.001). CONCLUSION: Quantitative optical coherence tomography-angiography alterations in the choriocapillaris microvascularization are an early biomarker of RR and are correlated to the severity of the disease.

SINGLE INJECTION RESPONSE TO ANTIVASCULAR ENDOTHELIAL GROWTH FACTOR AGENTS IN PATIENTS WITH WET AGE-RELATED MACULAR DEGENERATION: Incidence and Characteristics.

PURPOSE: To determine the incidence of complete resolution of choroidal neovascular membrane-associated exudation with a single antivascular endothelial growth factor injection in treatment-naive wet age-related macular degeneration patients and its associated characteristics. METHODS: Retrospective, observational study of naive wet age-related macular degeneration patients who received antivascular endothelial growth factor therapy with ranibizumab/aflibercept and demonstrated complete resolution of retinal exudation with a single injection. Complete resolution was defined as the total disappearance of the intraretinal fluid, cysts, and subretinal fluid and a return of retinal thickness to <250 µm on spectral-domain optical coherence tomography. All relevant data were collected. Follow-up was scheduled on Days 1, 7, and 30 postoperatively and then monthly, with at least 9 visits mandatory per year if the macula remained fluid free. Appropriate statistical analyses were performed. RESULTS: Sixty-three patients (29 men; mean age 67.25 ± 4.40 years) were identified. The mean baseline and final-corrected distance visual acuity was 20/160 and 20/45, respectively. Patients completed a mean of 10.9 follow-up visits per year. Smaller choroidal neovascular membranes (<200 µm), early presentation, better presenting corrected distance visual acuity, subfoveal choroidal neovascular membranes, absence of blood/fibrosis, and use of aflibercept (2 mg) favored resolution with one injection. CONCLUSION: A subset (13.76%; 63/458, 95% confidence intervals: 10.73-17.25) of patients with treatment-naive wet age-related macular degeneration demonstrates resolution of choroidal neovascular membrane-associated exudation with a single antivascular endothelial growth factor injection, sustained over 2 years or more. This can lower therapy costs, treatments, office visits, and the potential risk of geographic atrophy.

LONG-TERM INCIDENCE AND RISK FACTORS OF OCULAR HYPERTENSION FOLLOWING DEXAMETHASONE-IMPLANT INJECTIONS: THE SAFODEX-2 STUDY.

PURPOSE: To analyze the incidence, risk factors, and time to onset of ocular hypertension (OHT) after intravitreal injections (IVI) of dexamethasone implant and to evaluate the long-term cumulative probability of intraocular pressure elevation. METHODS: Eyes of patients having received at least one dexamethasone implant IVI between October 2010 and February 2015 were included in the present study. Ocular hypertension was defined as intraocular pressure > 25 mmHg and/or an increase of 10 mmHg over the follow-up period compared with baseline intraocular pressure. RESULTS: Four hundred ninety-four eyes were studied in 410 patients. For a total of 1,371 IVI, the incidence of OHT was 32.6% in the study eyes with a mean follow-up period of 30 months (3-62.5) and a median follow-up of 29 months. Pressure-lowering treatment was introduced for 36.9% of eyes. Topical treatment alone was sufficient to manage OHT in 97%. Young age, male sex, uveitis and retinal vein occlusion, and glaucoma treated with a double- or triple-combination topical pressure-lowering medication were found to be risk factors for OHT. The incidence of OHT did not change with an increase in the number of IVI, and there was no cumulative effect, defining by an increase of the incidence of OHT in patients after repeated IVI (P = 0.248). CONCLUSION: This study confirmed that OHT is of moderate incidence, transient, controlled by topical treatment and provides data on the long-term cumulative probability of intraocular pressure elevation in a large cohort of eyes treated with dexamethasone implant IVI. Repeat injections of dexamethasone implant neither increase nor decrease the risk of OHT.

QUANTITATIVE ANALYSIS OF CHORIOCAPILLARIS ALTERATIONS IN SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN DIABETIC PATIENTS.

PURPOSE: To evaluate quantitative alterations of the choriocapillaris in swept-source optical coherence tomography angiography in diabetic patients. METHODS: We included normal patients and diabetic patients with and without diabetic retinopathy (DR), excluding patients with macular edema. Angiograms in 3 × 3 mm were acquired with Plexelite 9000 swept-source optical coherence tomography angiography. Choroidal flow voids were analyzed after removal of projection artifacts. The main evaluation was the correlation between choroidal flow voids area (FVA-CC) and DR stage. RESULTS: A total of 120 eyes of 72 patients were analyzed. There were 17 eyes from healthy subjects, 30 eyes without DR, 22 eyes with minimal nonproliferative DR, 30 eyes with moderate nonproliferative DR, 16 eyes with severe nonproliferative DR, and 5 eyes with proliferative DR (PDR). The percentage of FVA-CC for each group was, respectively, 10.9 ± 3.4%, 14.6 ± 4.8%, 17.6 ± 3.5%, 20.7 ± 5.9%, 19.9 ± 2.9%, and 26.6 ± 4.4%. FVA-CC and DR stage significantly correlated (P < 0.0001). FVA-CC was significantly increased in diabetic patients without DR compared with healthy subjects (P = 0.008). CONCLUSION: Diabetes is associated with quantifiable choriocapillaris alterations in swept-source optical coherence tomography angiography. These alterations precede clinical signs of DR and are correlated with DR stage.

ENDOGENOUS ENDOPHTHALMITIS IN THE SETTING OF COVID-19 INFECTION: A Case Series.

PURPOSE: To describe endogenous endophthalmitis in the setting of COVID-19 pneumonia. METHODS: Patients recovering from COVID-19 pneumonia who presented to our department with any or all of the following complaints: pain, watering, redness, and decreased vision were identified. All relevant data were collected for analysis. RESULTS: Three patients with endogenous endophthalmitis were identified. All patients had been treated for COVID-19 pneumonia and therefore had received remdesivir and systemic steroids; 2 of the 3 patients received tocilizumab. All patients received vitreous biopsy, vitrectomy, and intraocular antibiotic injection. Patient 1 demonstrated Klebsiella pneumoniae in blood culture, K. pneumoniae and Escherichia coli in urine culture, and K. pneumoniae in vitreous fluid, whereas Patients 2 and 3 demonstrated Stenotrophomonas maltophilia and methicillin-resistant Staphylococcus aureus in the blood and nasopharyngeal culture, respectively. Correspondingly, the same organism was cultured from vitreous in Patients 2 and 3. The visual acuity at the last follow-up in Patients 1 to 3 was 20/100, 20/80, and 20/40, respectively. The probable source of infection was identified in each as renal calculi, dental caries, and the pharynx, respectively. Real-time polymerase chain reaction demonstrated the presence of Severe Acute Respiratory Syndrome Coronavirus 2 in the vitreous fluid of Patient 1. CONCLUSION: We report good outcomes of early intervention for endogenous endophthalmitis in the setting of COVID-19 infection. We also document the presence of SARS-CoV-2 in vitreous.

UVEITIS TREATED WITH DEXAMETHASONE IMPLANT.

PURPOSE: To evaluate the real-life efficacy and safety of the intravitreal dexamethasone implant in uveitis. METHODS: This retrospective observational multicentric study included 152 eyes treated exclusively by 358 dexamethasone implant injections. The main outcome measures included change in the best-corrected visual acuity, central macular thickness, and vitreous haze score. RESULTS: Patients were treated with dexamethasone implant for macular edema (51.3%), vitritis with macular edema (40.1%), vitritis (5.3%), and other causes (3.3%). The mean duration of follow-up was 19.0 months. The mean gain in best-corrected visual acuity during follow-up was +12.1 letters. An improvement in best-corrected visual acuity ≥5, 10, and 15 letters was found in 64.5, 50.7, and 35.5% of cases, respectively. 59.7% of eyes with macular edema at baseline were found to be anatomical responders. Vitritis resolution (vitreous haze = 0+) was obtained in 81.4% of cases. Ocular hypertension (intraocular pressure ≥25 mmHg and/or gain ≥10 mmHg from baseline) occurred in 28.3% of patients. No filtering surgery/laser therapy was required. A total of 40.2% of phakic subjects underwent cataract surgery on average 11.2 months after the first injection. CONCLUSION: This study confirms the efficacy and safety of the dexamethasone implant in noninfectious uveitis. Cataract and ocular hypertension were not uncommon but easily manageable.

COMPARATIVE EFFECTIVENESS OF PROTON BEAM VERSUS PHOTODYNAMIC THERAPY TO SPARE THE VISION IN CIRCUMSCRIBED CHOROIDAL HEMANGIOMA.

PURPOSE: The aim of this study was to compare the functional and anatomical effectiveness of photodynamic therapy (PDT) versus proton beam therapy (PBT) in a real-life setting for the treatment of circumscribed choroidal hemangioma. METHODS: A total of 191 patients with a diagnosis of circumscribed choroidal hemangioma and treated by PBT or PDT were included for analyses. RESULTS: The 119 patients (62.3%) treated by PDT were compared with the 72 patients treated by PBT. The final best-corrected visual acuity did not differ significantly between the two groups (P = 0.932) and final thickness was lower in the PBT compared with the PDT group (P = 0.001). None of the patients treated by PBT needed second-line therapy. In comparison, 53 patients (44.5%) initially treated by PDT required at least one other therapy and were associated with worse final best-corrected visual acuity (P = 0.037). In multivariate analysis, only an initial thickness greater than 3 mm remained significant (P = 0.01) to predict PDT failure with an estimated odds ratio of 2.72, 95% confidence interval (1.25-5.89). CONCLUSION: Photodynamic therapy and PBT provide similar anatomical and functional outcomes for circumscribed choroidal hemangioma ≤3 mm, although multiple sessions are sometimes required for PDT. For tumors >3 mm, PBT seems preferable because it can treat the tumor in only 1 session with better functional and anatomical outcomes.

HYPERAUTOFLUORESCENT SPOTS IN ACUTE OCULAR TOXOPLASMOSIS: A New Indicator of Outer Retinal Inflammation.

PURPOSE: The aim of this study was to describe the fundus autofluorescence patterns in acute ocular toxoplasmosis (OT) and to correlate these findings with other imaging. METHODS: A retrospective multicenter case series of 27 eyes from 27 patients with acute onset of posterior OT was conducted. Multimodal imaging including fundus autofluorescence was performed at diagnosis and during follow-up. RESULTS: All OT lesions were hypoautofluorescent on fundus autofluorescence imaging. Fourteen patients (51.8%) also had hyperautofluorescent spots around the active foci that disappeared after retinal photobleaching. Although these spots were not seen on early phase of indocyanine green angiography, they become hypofluorescent in the late phase without choriocapillaris flow impairment on optical coherence tomography angiography. On B-scan spectral domain optical coherence tomography, spots corresponded to outer retinal alterations in all cases. All hyperautofluorescent spots disappeared during follow-up as acute OT resolved. Younger patients and those with more posterior inflammatory symptoms (vasculitis and/or papillitis) were more frequent with the presence of hyperautofluorescent spots. CONCLUSION: Ocular toxoplasmosis may trigger a transient outer retinal disruption in eyes with marked inflammatory symptoms of the younger patients.

Current role of intravitreal injections in Irvine Gass syndrome-CRIIG study.

OBJECTIVE: To analyze the role of intravitreal anti-vascular endothelial growth factor (anti-VEGF) or steroid injection for the management of Irvine Gass syndrome. METHODS: It is an interventional, retrospective, multicenter study. One hundred and thirty-two injections were given in 79 eyes of 72 patients with Irvine Gass syndrome. Patients were treated with at least one intravitreal injection of either anti-VEGF or steroid. Outcomes were measured at 12 months (± 1 week). [Ranibizumab (Lucentis; Genentech, South San Francisco, CA) (Razumab; Intas Pharmaceutical Ltd, Ahmedabad, India) Bevacizumab (Avastin; Genentech, South San Francisco, CA) or Aflibercept (Eylea; Regeneron, Tarrytown, NY)] or steroids [Dexamethasone implant (Ozurdex, Allergan Inc, Irvine, CA) or intravitreal triamcinolone)]. RESULTS: Intravitreal injections were initiated in (67.6%) of eyes within 14 weeks of diagnosis. Intravitreal dexamethasone implant was used as the initial intravitreal therapy in (73.4%) of eyes. More than fifty percent (54.5%) of the patients were switched from anti-VEGF to Intravitreal dexamethasone implant. Reduction in the mean CMT was 336.7 ± 191.7 and 160.1 ± 153.1 microns in eyes treated within four weeks and more than 14 weeks from diagnosis (p = 0.005). Mean ETDRS letter gain was 16.7 ± 12.9 and 5.2 ± 9.2 in eyes treated within 4 weeks and more than 14 weeks from diagnosis (p = 0.004). Three eyes injected with intravitreal dexamethasone implant reported an intraocular pressure spike of > 25 mmHg which was controlled with topical medications. No other ocular or systemic adverse events were observed. CONCLUSION: Study results suggest that physicians tend to introduce intravitreal therapy within 14 weeks of diagnosis. The most common therapy at initiation and for the switch is intravitreal dexamethasone implant. Patients treated early (within 4 weeks) respond better in terms of structure and function.