Fungal Endophthalmitis Masquerading as Sympathetic Ophthalmia.

PURPOSE: To describe the ocular pathology of a patient with fungal endophthalmitis with features mimicking sympathetic ophthalmia. METHODS: Review of medical records and histopathology of a single patient. RESULTS: A 72-year-old male who sustained penetrating injury to the left eye with an agave plant presented to our clinic 16 months after the initial injury. Prior to presentation, the patient had developed endophthalmitis and had undergone anterior chamber washout, vitrectomy, and intravitreal steroids, antibiotics, antifungals, and anti-vascular endothelial growth factor (VEGF) therapy. At presentation, the patient had a blind, painful eye and subsequently underwent enucleation. Histopathology demonstrated granulomatous inflammation with multinucleated giant cells in the iris and Dalen Fuchs nodules with CD68 positive epithelioid histiocytes associated with the retinal pigment epithelium (RPE) sparing the choriocapillaris. These findings were initially attributed to sympathetic ophthalmia. The fellow eye did not have any signs of inflammation, and additional fungal PAS stains were positive for filamentous fungal elements, leading to a diagnosis of fungal endophthalmitis. CONCLUSIONS: Fungal endophthalmitis may develop histopathologic features that are similar to those seen in sympathetic ophthalmia. Recognition of the overlap between the histopathologic features of these diseases may reduce the possibility of misdiagnosis and unnecessary treatment of the fellow eye.

Long-Term Retinal Vascular Changes in Age-Related Macular Degeneration Measured Using Optical Coherence Tomography Angiography.

BACKGROUND AND OBJECTIVE: To determine if age-related macular degeneration (AMD) status affects longitudinal retinal vessel changes. PATIENTS AND METHODS: Retrospective, cohort study of 125 eyes (75 patients) with AMD, following retinal vessel density (VD) and foveal avascular zone (FAZ) measurements using optical coherence tomography angiography (OCT-A) over 24 months. RESULTS: FAZ area (P < .001) and perimeter (P < .001) increased over 2 years, with no difference between nonexudative and exudative AMD (P = .134-.976). Eyes with geographic atrophy (GA) showed greater progressive VD loss (P = .023-.038), and greater increase in FAZ area (P = .044) and perimeter (P = .040) compared to eyes without GA. Neither baseline nor 2-year change in vascular parameters were associated with choroidal neovascularization (CNV) or GA incidence in nonexudative AMD, or anti-VEGF injection frequency in exudative AMD (P = .070-.952). CONCLUSION: AMD eyes with GA undergo more rapid loss of retinal vessel density and FAZ enlargement over 2 years, suggesting a relationship between the retinal vasculature and AMD pathophysiology. [Ophthalmic Surg Lasers Imaging Retina 2022;53:529-536.].

Analysis of the retinal capillary plexus layers in a murine model with diabetic retinopathy: effect of intravitreal injection of human CD34+ bone marrow stem cells.

BACKGROUND: Diabetic retinopathy is a retinal vasculopathy involving all three retinal capillary plexus layers. Since human CD34+ bone marrow stem cells (BMSCs) have the potential to promote revascularization of ischemic tissue, this study tests the hypothesis that intravitreal injection of human CD34+ BMSCs can have protective effects on all layers of the retinal vasculature in eyes with diabetic retinopathy. METHODS: Streptozotocin (STZ)-induced diabetic mice were injected intravitreally with 50,000 human CD34+ BMSCs or phosphate-buffered saline (PBS) into the right eye. Systemic immunosuppression with rapamycin and tacrolimus was started 5 days before the injection and maintained for study duration to prevent rejection of human cells. All mice were euthanized 4 weeks after intravitreal injection; both eyes were enucleated for retinal flat mount immunohistochemistry. The retinal vasculature was stained with Isolectin-GS-IB4. Confocal microscopy was used to image four circular areas of interest of retina, 1-mm diameter around the optic disc. Images of superficial, intermediate, and deep retinal capillary plexus layers within the areas of interest were obtained and analyzed using ImageJ software with the Vessel Analysis plugin to quantitate the retinal vascular density and vascular length density in the three plexus layers. RESULTS: Three distinct retinal capillary plexus layers were visualized and imaged using confocal microscopy. Eyes that received intravitreal injection of CD34+ BMSCs (N=9) had significantly higher vascular density and vascular length density in the superficial retinal capillary plexus when compared to the untreated contralateral eyes (N=9) or PBS treated control eyes (N=12; P values <0.05 using ANOVA followed by post-hoc tests). For the intermediate and deep plexus layers, the difference was not statistically significant. CONCLUSIONS: The protective effect of intravitreal injection of the human CD34+ BMSCs on the superficial retinal capillary plexus layers is demonstrated using confocal microscopy in this murine model of diabetic retinopathy.

Subretinal versus intravitreal administration of human CD34+ bone marrow-derived stem cells in a rat model of inherited retinal degeneration.

BACKGROUND: To evaluate whether subretinal or intravitreal injection of human CD34+ bone marrow-derived stem cells (BMSC) can have protective effects on retinal degeneration that may be enhanced by coadministration of exosomes harvested from human bone marrow mesenchymal stem cells (MSCs). METHODS: Human CD34+ cells were harvested from the mononuclear cell fraction of bone marrow using magnetic beads and labeled with EGFP. Exosomes were harvested from cultured human MSCs under hypoxic conditions. Royal College of Surgeons (RCS) 3-weeks-old rats, immunosuppressed with cyclosporine A, received subretinal or intravitreal injection of CD34+ cells (50,000 cells), CD34+ cells with exosomes (50,000 cells+10 µg), exosomes alone (10 µg), or PBS. Retinal function was examined using electroretinography (ERG), and the eyes were harvested for histologic and immunohistochemical analysis. RESULTS: The b-wave amplitude of ERG at 2 weeks after injection was significantly higher in eyes with subretinal or intravitreal CD34+ BMSC alone or in combination with exosomes when compared to PBS injected eyes or untreated contralateral eyes. At 4 weeks after injection, the ERG signal decreased in all groups but eyes with subretinal CD34+ BMSCs alone or combined with exosomes showed partially preserved ERG signal and preservation of the outer nuclear layer of the retina near the injection site on histology when compared to eyes with PBS injection. Immunohistochemical analysis identified the human cells in the outer retina. Subretinal or intravitreal exosome injection had no effect on retinal degeneration when administered alone or in combination with CD34+ cells. CONCLUSIONS: Both subretinal and intravitreal injection of human CD34+ BMSCs can provide functional rescue of degenerating retina, although the effects were attenuated over time in this rat model. Regional preservation of the outer retina can occur near the subretinal injection site of CD34+ cells. These results suggest that CD34+ cells may have therapeutic potential in retinal degeneration.

Intraoperative Retinal Changes May Predict Surgical Outcomes After Epiretinal Membrane Peeling.

Purpose: To investigate whether intraoperative retinal changes during epiretinal membrane (ERM) peeling affect anatomic or functional outcomes after surgery. Methods: We measured retinal thickness using an intraoperative optical coherence tomography (iOCT) device in patients undergoing pars plana vitrectomy with membrane peeling for idiopathic ERM. Changes in intraoperative central macular thickness (iCMT) were compared with postoperative improvements in CMT and best-corrected visual acuity (VA). Results: Twenty-seven eyes from 27 patients (mean age 68 years) underwent iOCT-assisted ERM peeling surgery. Before surgery, mean VA was logMAR 0.50 ± 0.36 (Snellen 20/63), and mean baseline CMT was 489 ± 82 µm. Mean iCMT before peeling was 477 ± 87 µm, which correlated well with preoperative CMT (P < 0.001). Mean change in iCMT was -39.6 ± 37 µm (range -116 to +77 µm). After surgery, VA improved to logMAR 0.40 ± 0.38 (Snellen 20/50) at month 1 and logMAR 0.27 ± 0.23 (Snellen 20/37) at month 3, whereas CMT decreased to 397 ± 44 µm and 396 ± 51 µm at months 1 and 3. Eyes that underwent greater amount of iCMT change (absolute value of iCMT change) were associated with greater CMT reduction at month 1 (P < 0.001) and month 3 (P = 0.010), whereas those with greater intraoperative thinning (actual iCMT change) showed a trend toward better VA outcomes at months 1 (P = 0.054) and 3 (P = 0.036). Conclusions: Intraoperative changes in retinal thickness may predict anatomic and visual outcomes after idiopathic ERM peeling surgery. Translational Relevance: Our study suggests that intraoperative retinal tissue response to ERM peeling surgery measured by iOCT may be a prognostic indicator for restoration of retinal architecture and for visual acuity outcomes.

Ocular Outcomes after Treatment of Cytomegalovirus Retinitis Using Adoptive Immunotherapy with Cytomegalovirus-Specific Cytotoxic T Lymphocytes.

PURPOSE: To describe ocular outcomes in eyes with cytomegalovirus (CMV) retinitis treated with adoptive immunotherapy using systemic administration of CMV-specific cytotoxic Tlymphocytes (CMV-specific CTLs). DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with active CMV retinitis evaluated at a tertiary care academic center. METHODS: Treatment of CMV retinitis with standard-of-care therapy (systemic or intravitreal antivirals) or CMV-specific CTLs (with or without concurrent standard-of-care therapies). MAIN OUTCOME MEASURES: The electronic medical record was reviewed to determine baseline characteristics, treatment course, and ocular outcomes, including best-corrected visual acuity (BCVA), treatments administered (CMV-specific CTLs, systemic antivirals, intravitreal antivirals), resolution of CMV retinitis, any occurrence of immune recovery uveitis, cystoid macular edema, retinal detachment, or a combination thereof. RESULTS: Seven patients (3 of whom had bilateral disease [n = 10 eyes]) were treated with CMV-specific CTLs, whereas 20 patients (6 of whom had bilateral disease [n = 26 eyes]) received standard-of-care treatment. Indications for CMV-specific CTL therapy included persistent or progressive CMV retinitis (71.4% of patients); CMV UL54 or UL97 antiviral resistance mutations (42.9%); side effects or toxicity from antiviral agents (57.1%); patient intolerance to longstanding, frequent antiviral therapy for persistent retinitis (28.6%); or a combination thereof. Two patients (28.6%; 4 eyes [40%]) received CMV-specific CTL therapy without concurrent systemic or intravitreal antiviral therapy for active CMV retinitis, whereas 5 patients (71.4%; 6 eyes [60%]) continued to receive concurrent antiviral therapies. Resolution of CMV retinitis was achieved in 9 eyes (90%) treated with CMV-specific CTLs, with BCVA stabilizing (4 eyes [40%]) or improving (4 eyes [40%]) in 80% of eyes over an average follow-up of 33.4 months. Rates of immune recovery uveitis, new-onset cystoid macular edema, and retinal detachment were 0%, 10% (1 eye), and 20% (2 eyes), respectively. These outcomes compared favorably with a nonrandomized cohort of eyes treated with standard-of-care therapy alone, despite potentially worse baseline characteristics. CONCLUSIONS: CMV-specific CTL therapy may represent a novel monotherapy or adjunctive therapy, or both, for CMV retinitis, especially in eyes that are resistant, refractory, or intolerant of standard-of-care antiviral therapies. More generally, adoptive cell transfer and adoptive immunotherapy may have a role in refractory CMV retinitis. Larger prospective, randomized trials are necessary.

NATURAL HISTORY AND PREDICTORS OF VISION LOSS IN EYES WITH DIABETIC MACULAR EDEMA AND GOOD INITIAL VISUAL ACUITY.

PURPOSE: To identify clinical and anatomic factor-associated vision loss in eyes with treatment-naïve diabetic macular edema and good initial visual acuity. METHODS: Retrospective cohort study after long-term history of eyes with untreated center-involving diabetic macular edema and baseline visual acuity ≥ 20/25 seen at the University of California, Davis Eye Center between March 2007 and March 2018. We collected characteristics including diabetes type, hemoglobin A1c, presence of visual symptoms, visual acuity, and diabetic retinopathy severity; and spectral-domain optical coherence tomography biomarkers including central subfield thickness, intraretinal cyst size, intraretinal hyperreflective foci, disorganization of retinal inner layers, and outer layer disruptions to determine factors associated with vision loss as defined by DRCR Protocol V as threshold for initiating aflibercept therapy. RESULTS: Fifty-six eyes (48 patients) with untreated diabetic macular edema and mean baseline visual acuity of logMAR 0.05 ± 0.05 (Snellen 20/22) were followed for an average of 5.1 ± 3.3 years, with a median time to vision loss of 465 days (15 months). Older age (hazard ratio [HR] 1.04/year, P = 0.0195) and eyes with severe NPDR (HR 3.0, P = 0.0353) or proliferative diabetic retinopathy (HR 7.7, P = 0.0008) had a higher risk of a vision loss event. None of the spectral-domain optical coherence tomography biomarkers were associated with vision loss except central subfield thickness (HR 0.98, P = 0.0470) and cyst diameter (HR 1.0, P = 0.0094). CONCLUSION: In eyes with diabetic macular edema and good initial vision, those with older age and worse diabetic retinopathy severity should be monitored closely for prompt treatment initiation when vision loss occurs.

Phase I/II randomized study of proton beam with anti-VEGF for exudative age-related macular degeneration: long-term results.

BACKGROUND/OBJECTIVE: To determine if treatment of exudative age-related macular degeneration (eAMD) using proton beam therapy (PBT) combined with intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy is safe and effective long term. SUBJECT/METHODS: Thirty eyes with newly diagnosed eAMD were enrolled in a phase I/II prospective, sham-controlled double-masked university study. Eyes were randomized 1:1:1-24 GyE, 16 GyE or sham radiation, and treated with three initial monthly intravitreal ranibizumab or bevacizumab. Subsequent anti-VEGF reinjection was based on monthly optical coherence tomography and examination for 2 years and standard of care thereafter. RESULTS: A total of 23 eyes completed 2-year study follow-up, of which 16 maintained monthly follow-up. Mean best-correct visual acuity (BCVA) at 2 years was similar among treatment groups (p > 0.05). The 24 GyE group required fewer anti-VEGF injections when compared with the sham group at 2 years (4.67 ± 1.9 vs 9.67 ± 3.5; p = 0.017). Extended follow-up (mean 4 years) available in 22 eyes showed persistent reduced need for anti-VEGF therapy among eyes treated with 24 GyE compared with sham radiation (2.0 ± 1.6 vs 4.84 ± 2.4 per year, p = 0.008). New and increasing geographic atrophy (GA), noted in some eyes in all treatment groups, resulted in decreased mean BCVA from baseline for the 24 GyE group on extended follow-up (p = 0.009). Possible mild radiation retinopathy noted in 15% of eyes was not visually significant. CONCLUSIONS: Initial treatment combining PBT (24 GyE) with intravitreal anti-VEGF therapy appears to decrease the need for anti-VEGF reinjection in eyes with newly diagnosed eAMD. Radiation retinopathy risk was low and does not appear visually significant. Long-term vision was limited by GA development especially in the 24 GyE group.

Identification of Patients with Pentosan Polysulfate Sodium-Associated Maculopathy through Screening of the Electronic Medical Record at an Academic Center.

AIMS: This chart review of a quaternary academic medical center electronic medical record (EMR) aimed to identify patients at risk of development of maculopathy with exposure to pentosan polysulfate sodium (PPS). METHODS: A review of electronic medical records of a quaternary medical center of patients with either documented exposure to PPS or diagnosis of interstitial cystitis (IC) from 2007 to 2019 was performed for retinal imaging and visual acuity; the study was conducted in August of 2019. RESULTS: 216 charts were included for analysis, of which 96 had documented eye exams and 24 had retinal imaging done. We identified three patients with maculopathy in the context of long-term exposure to PPS via chart review, and one additional patient was identified by referral. The median PPS exposure duration was 11 years (range 7 to 19 years). Median logMAR BCVA OD 0.6 range was 0.0-1.9 (approximate Snellen equivalent 20/80 range (20/20-20/1600)) and OS 0.7 range was 0.1-1.9 (approximate Snellen equivalent 20/100 range (20/25-20/1600)). Ultrawidefield color fundus imaging and fundus autofluorescence revealed findings of pigmentary changes and patchy macular atrophy. Optical coherence tomography (OCT) demonstrated outer retinal thinning and increased choroidal transmission coincident with areas of atrophy seen on fundus imaging. CONCLUSIONS: Less than half of patients at risk for development of maculopathy due to exposure to PPS had received eye examinations, suggesting that those at risk are not receiving adequate screening. We found two patients with PPS maculopathy who had relatively preserved central vision, one patient with bitemporal vision loss, and one patient who developed vision loss in both eyes.

Retinal stem cell transplantation: Balancing safety and potential.

Stem cell transplantation holds great promise as a potential treatment for currently incurable retinal degenerative diseases that cause poor vision and blindness. Recently, safety data have emerged from several Phase I/II clinical trials of retinal stem cell transplantation. These clinical trials, usually run in partnership with academic institutions, are based on sound preclinical studies and are focused on patient safety. However, reports of serious adverse events arising from cell therapy in other poorly regulated centers have now emerged in the lay and scientific press. While progress in stem cell research for blindness has been greeted with great enthusiasm by patients, scientists, doctors and industry alike, these adverse events have raised concerns about the safety of retinal stem cell transplantation and whether patients are truly protected from undue harm. The aim of this review is to summarize and appraise the safety of human retinal stem cell transplantation in the context of its potential to be developed into an effective treatment for retinal degenerative diseases.

Real-world management and long-term outcomes of diabetic macular oedema with good visual acuity.

PURPOSE: To evaluate the management and long-term outcomes of patients with diabetic macular oedema (DMO) and good initial visual acuity in real-world settings. METHODS: We reviewed 122 eyes of 100 patients with treatment-naive DMO and initial best-corrected visual acuity (BCVA) of 20/25 or better. We assessed clinical characteristics, logMAR BCVA, central subfield thickness (CST), cumulative intravitreal injections and laser treatments at yearly intervals, and characteristics at time of initial treatment. Linear mixed effects models were used to identify predictors of visual outcomes. RESULTS: At presentation, mean BCVA was 0.057 ± 0.048 logMAR (Snellen 20/23) and mean CST was 288 ± 57 µm. After a median follow-up of 3 years, 51% of eyes underwent treatment. More eyes underwent intravitreal injection as initial treatment (54%), but lasers were initiated at an earlier time and at better BCVA. Final BCVA was associated with better BCVA (P < 0.001) and earlier timing (P = 0.017) at initial treatment, but not CST at first treatment (P = 0.634) or cumulative number of injections or lasers (P = 0.441-0.606). CONCLUSION: DMO with good initial visual acuity should be monitored closely, as delay in treatment initiation is associated with worse visual outcomes. BCVA at time of initial treatment is the strongest determinant of final visual acuity.

Effects of intravitreal injection of human CD34+ bone marrow stem cells in a murine model of diabetic retinopathy.

Human CD34 + stem cells are mobilized from bone marrow to sites of tissue ischemia and play an important role in tissue revascularization. This study used a murine model to test the hypothesis that intravitreal injection of human CD34 + stem cells harvested from bone marrow (BMSCs) can have protective effects in eyes with diabetic retinopathy. Streptozotocin-induced diabetic mice (C57BL/6J) were used as a model for diabetic retinopathy. Subcutaneous implantation of Alzet pump, loaded with Tacrolimus and Rapamycin, 5 days prior to intravitreal injection provided continuous systemic immunosuppression for the study duration to avoid rejection of human cells. Human CD34 + BMSCs were harvested from the mononuclear cell fraction of bone marrow from a healthy donor using magnetic beads. The CD34 + cells were labeled with enhanced green fluorescent protein (EGFP) using a lentiviral vector. The right eye of each mouse received an intravitreal injection of 50,000 EGFP-labeled CD34 + BMSCs or phosphate buffered saline (PBS). Simultaneous multimodal in vivo retinal imaging system consisting of fluorescent scanning laser ophthalmoscopy (enabling fluorescein angiography), optical coherence tomography (OCT) and OCT angiography was used to confirm the development of diabetic retinopathy and study the in vivo migration of the EGFP-labeled CD34 + BMSCs in the vitreous and retina following intravitreal injection. After imaging, the mice were euthanized, and the eyes were removed for immunohistochemistry. In addition, microarray analysis of the retina and retinal flat mount analysis of retinal vasculature were performed. The development of retinal microvascular changes consistent with diabetic retinopathy was visualized using fluorescein angiography and OCT angiography between 5 and 6 months after induction of diabetes in all diabetic mice. These retinal microvascular changes include areas of capillary nonperfusion and late leakage of fluorescein dye. Multimodal in vivo imaging and immunohistochemistry identified EGFP-labeled cells in the superficial retina and along retinal vasculature at 1 and 4 weeks following intravitreal cell injection. Microarray analysis showed changes in expression of 162 murine retinal genes following intravitreal CD34 + BMSC injection when compared to PBS-injected control. The major molecular pathways affected by intravitreal CD34 + BMSC injection in the murine retina included pathways implicated in the pathogenesis of diabetic retinopathy including Toll-like receptor, MAP kinase, oxidative stress, cellular development, assembly and organization pathways. At 4 weeks following intravitreal injection, retinal flat mount analysis showed preservation of the retinal vasculature in eyes injected with CD34 + BMSCs when compared to PBS-injected control. The study findings support the hypothesis that intravitreal injection of human CD34 + BMSCs results in retinal homing and integration of these human cells with preservation of the retinal vasculature in murine eyes with diabetic retinopathy.

Ultrasonography and transillumination for uveal melanoma localisation in proton beam treatment planning.

BACKGROUND/OBJECTIVE: The success of proton beam treatment (PBT) in uveal melanoma depends in part on the accuracy of tumour localisation. This study determined if using ultrasonography (US) to measure the distance between tumour margin and tantalum ring (DTR) in PBT planning improves local treatment success when compared with using intraoperative transillumination (TI) alone. METHODS: Retrospective analysis of patients with uveal melanoma treated at one centre between January 2006 and June 2017 with ≥12-month follow-up (or until treatment failure). Local tumour control was compared among study groups based on methods for measuring DTR: Group 1 (TI alone), Group 2A (postoperative US alone) and Group 2B (combination). RESULTS: Fifty-four eyes (54 patients) with uveal melanomas were included: Group 1 (22 eyes, 41%), Group 2A (11 eyes, 20%) and Group 2B (21 eyes, 39%). Mean age at diagnosis was 64 years [median 66 years, range 23-86 years]. Fifty tumours (93%) involved the choroid, while four involved the ciliary body (7%). In Group 2B, PBT treatment was based on the DTR obtained using US; DTR differed between TI and US by ≥1 mm for 25 rings in 16 eyes and ≥2 mm for 12 rings in 7 eyes. Five-year Kaplan-Meier estimate revealed a difference in local treatment success between Groups 1 and 2, (0.82 vs. 1.0, p = 0.02) with no difference in overall survival estimate, (0.85 vs. 0.83, p = 0.8). CONCLUSIONS: US can be used to measure DTR in PBT planning for uveal melanoma. This may improve accuracy of tumour localisation and improve local treatment success.

Posterior Segment Complications and Impact on Long-Term Visual Outcomes in Eyes With a Type 1 Boston Keratoprosthesis.

PURPOSE: To determine the spectrum of retinal complications (RCs) in a cohort of eyes with a type 1 Boston keratoprosthesis (KPro). METHODS: All patients (36 eyes of 31 patients) who received a type 1 Boston KPro from January 2004 to December 2015 at the University of California, Davis, were included. Electronic medical records were reviewed for relevant clinical data. Demographic information, initial corneal diagnosis, postoperative course, posterior segment complications, preoperative and final visual acuity were tabulated and analyzed. RESULTS: Posterior segment complications after type 1 Boston KPro were identified in 56% of eyes (n = 20). They included retinal detachment (n = 11; 31%), retroprosthetic membrane (n = 10; 28%), endophthalmitis (n = 7; 19%), cystoid macular edema (n = 5; 14%), epiretinal membrane (n = 4; 11%), vitreous hemorrhage (n = 2; 6%), choroidal detachment (n = 2; 6%), retinal vein occlusion (n = 1; 3%), and macular hole (n = 1; 3%). During the average follow-up period of 53.8 months (median, 57.1 months; range, 1.8-108.7 months) after type 1 Boston KPro, final best-corrected visual acuity improved by a mean of 0.12 logarithm of the minimum angle of resolution (LogMAR) units (range, -2.26 to +2.26) overall. The proportion of eyes with final best-corrected visual acuity better than 20/200 was 2 of 20 (10%) in the group with RCs, in contrast to 7 of 16 eyes (44%) noted among eyes without RCs. CONCLUSIONS: Long-term visual outcomes in eyes after type 1 Boston KPro may depend, in part, on maintaining a healthy posterior pole. Retinal detachment, in particular, may represent a threat to ultimate visual functioning. Regular examination of the peripheral fundus is recommended.

Long-term natural history of idiopathic epiretinal membranes with good visual acuity.

BACKGROUND/OBJECTIVES: To evaluate the long-term progression of idiopathic epiretinal membranes (iERMs) with good baseline visual acuity, and to identify predictors of visual decline. DESIGN: Retrospective case series SUBJECTS METHODS: We reviewed records of 145 eyes with iERM and best-corrected visual acuity (BCVA) of 20/40 or greater at presentation, including BCVA, lens status, and central macular thickness (CMT) at yearly visits; as well as anatomic biomarkers including vitreomacular adhesion, pseudohole, lamellar hole, intraretinal cysts, disorganization of the inner retinal layers (DRIL), and disruption of outer retinal layers. Linear mixed effects and mixed-effects Cox proportional hazards models were used to identify clinical and anatomic predictors of vision change and time to surgery. RESULTS: At presentation, mean BCVA was 0.17 ± 0.10 logMAR units (Snellen 20/30) and mean CMT was 353.3 ± 75.4 µm. After a median follow-up of 3.7 years (range 1-7 years), BCVA declined slowly at 0.012 ± 0.003 logMAR units/year, with phakic eyes declining more rapidly than pseudophakic eyes (0.019 ± 0.003 vs. 0.010 ± 0.004 logMAR units/year). Metamorphopsia, phakic lens status, lamellar hole, and inner nuclear layer cysts were associated with faster visual decline. Cumulative rates of progression to surgery were 2.9, 5.6, 12.2, and 21.1% at years 1-4. Visual symptoms, metamorphopsia, greater CMT, and disruption of outer retinal layers were associated with greater hazard for surgery. CONCLUSION: Eyes with iERM and visual acuity ≥ 20/40 experience slow visual decline, with 21% of eyes requiring surgery after 4 years. Clinical and anatomic predictors of vision loss may be distinct from factors associated with earlier surgical intervention.

OUTCOMES OF PNEUMATIC RETINOPEXY PERFORMED BY VITREORETINAL FELLOWS.

PURPOSE: To evaluate the anatomical and visual outcomes of patients who underwent pneumatic retinopexy by vitreoretinal fellows. METHODS: We included 198 eyes (198 patients) that underwent pneumatic retinopexy by vitreoretinal fellows at a single academic institution between November 2002 and June 2016. Main outcomes were single-operation success and final anatomical success in retinal reattachment, as well as visual acuity at 3 months and 6 months after treatment. RESULTS: Single-operation success rate was 63.6% at 3 months and 59.5% at 6 months. Final anatomical reattachment was achieved in 92.9% (n = 184) and 96.6% (n = 143) at 3 months and 6 months, respectively. Logarithm of the minimum angle of resolution visual acuity improved from 0.72 ± 0.1 (∼20/100 Snellen) at baseline to 0.36 ± 0.06 (∼20/40 Snellen) at 6 months (P < 0.001). There was no statistical difference in anatomical success rates or visual outcomes between cases performed by first- or second-year fellows (P > 0.50). Single-operation success was associated only with size of detachment (P = 0.01). Visual outcome was associated with macula status at baseline (P = 0.032) and number of reoperations (P < 0.001). CONCLUSION: Anatomical and visual outcomes of fellow-performed pneumatic retinopexy are comparable with those reported in the previous literature.

Protective Effect of Intravitreal Administration of Exosomes Derived from Mesenchymal Stem Cells on Retinal Ischemia.

PURPOSE: Exosomes derived from human mesenchymal stem cells (hMSCs) cultured under hypoxic conditions contain proteins and growth factors that promote angiogenesis. This study investigated the effect of intravitreal administration of these exosomes on retinal ischemia using a murine model. METHODS: Oxygen-induced retinopathy (OIR) was induced by exposing one-week-old male C57BL/6J mice to 5 days of 75% hyperoxic conditioning, and returning to room air. After hyperoxic conditioning, the right eye of each mouse was injected intravitreally with 1 µl saline or exosomes derived from hMSCs and compared to control mice of the same age raised in room air without OIR injected intravitreally with saline. Two weeks post-injection, fluorescein angiography (FA) and phase-variance optical coherence tomography angiography (pvOCTA) were used to assess retinal perfusion. Retinal thickness was determined by OCT. The extent of retinal neovascularization was quantitated histologically by counting vascular nuclei on the retinal surface. RESULTS: Among eyes with OIR, intravitreal exosome treatment partially preserved retinal vascular flow in vivo and reduced associated retinal thinning; retinal thickness on OCT was 111.1 ± 7.4µm with saline versus 132.1 ± 11.6µm with exosome, p < 0.001. Retinal neovascularization among OIR eyes was reduced with exosome treatment when compared to saline-treated eyes (7.75 ± 3.68 versus 2.68 ± 1.35 neovascular nuclei per section, p < 0.0001). No immunogenicity or ocular/systemic adverse effect was associated with intravitreal exosome treatment. CONCLUSIONS: Intravitreal administration of exosomes derived from hMSCs was well tolerated without immunosuppression and decreased the severity of retinal ischemia in this murine model. This appealing novel non-cellular therapeutic approach warrants further exploration.

Phase I/II Randomized Study of Proton Beam with Anti-Vascular Endothelial Growth Factor for Exudative Age-Related Macular Degeneration: One-Year Results.

OBJECTIVE: To assess the safety and efficacy of proton beam therapy (PBT) as an adjunct to intravitreal anti-vascular endothelial growth factor (VEGF) for the treatment of exudative age-related macular degeneration. DESIGN: Phase I/II, interventional, prospective, randomized, sham-controlled double-blinded study. PARTICIPANTS: Eyes with newly diagnosed exudative age-related macular degeneration with vision between 20/40 and 20/400 were included. Exclusion criteria included diabetes or other ocular comorbidities affecting vision. METHODS: Eyes were randomized to receive either 16 GyE, 24 GyE, or sham PBT. All eyes had 3 monthly intravitreal anti-VEGF treatments, followed by monthly visits with treatments as needed. MAIN OUTCOME MEASURES: Mean change in best-corrected visual acuity (BCVA), mean number of anti-VEGF injections, proportion of eyes with >15 letters BCVA decrease, proportion of eyes developing radiation retinopathy or papillopathy, proportion of eyes with cataract progression, and mean changes central retinal thickness on OCT and lesion size on angiography at 1 year. RESULTS: Of 30 enrolled eyes, 22 completed follow-up monthly for 12 months for analysis. The BCVA improved by a mean of 8 letters (0.48±0.36 logarithm of the minimum angle of resolution) overall from baseline. Overall, central retinal thickness decreased from 340±155 to 246±48 (P = 0.008) at 12 months. The mean change in BCVA and central retinal thickness was not different among the 3 study groups. The mean number of anti-VEGF injections at 12 months was 6.13 for sham irradiation arm, 5.52 in the 16 GyE arm, and 3.83 for the 24 GyE arm (P = 0.004 between sham and 24 GyE). No eye had severe visual loss, radiation retinopathy, or papillopathy. CONCLUSIONS: No safety issue was noted associated with combining 16 GyE or 24 GyE PBT with intravitreal anti-VEGF therapy in eyes with exudative age-related macular degeneration. Overall improvements in BCVA and imaging parameters were not affected by the addition of PBT, but the number of anti-VEGF treatments needed was significantly lower with the addition of 24 GyE PBT.