Surgical Management of Full-Thickness Macular Holes in Macular Telangiectasia Type 2: A Global Multicenter Study.

PURPOSE: To report on macular hole repair in macular telangiectasia type 2 (MacTel2). DESIGN: Global, multicenter, retrospective case series. PARTICIPANTS: Patients undergoing surgery for MacTel2-associated full-thickness macular hole (MTMH). METHODS: Standardized data collection sheet distributed to all surgeons. MAIN OUTCOME MEASURES: Anatomic closure and visual outcomes of MTMH. RESULTS: Sixty-three surgeries in 47 patients with MTMH were included from 30 surgeons. Mean age was 68.1 years, with 62% female, 72% White, 21% East or South Asian, 2% African American, and 2% Hispanic or Latino. Procedures included 34 internal limiting membrane (ILM) peeling alone, 22 ILM flaps, 5 autologous retinal transplantations (ARTs), 1 retinotomy, and 1 subretinal bleb. For ILM peeling, preoperative visual acuity (VA) was 0.667 ± 0.423 logarithm of the minimum angle of resolution (logMAR). Minimum hole diameter (MHD) was 305.5 ± 159.4 µm (range, 34-573 µm). Sixteen of 34 ILM peels (47%) resulted in MTMH closure. At postoperative month 6, VA was stable at 0.602 ± 0.516 logMAR (P = 0.65). VA improved by at least 2 lines in 43% and at least 4 lines in 24%. For ILM flaps, preoperative VA was 0.878 ± 0.552 logMAR. MHD was 440.8 ± 175.5 µm (range, 97-697 µm), which was significantly larger than for ILM peels (P < 0.01). Twenty of 22 ILM flaps (90%) resulted in MTMH closure, which was significantly higher than for ILM peels (P < 0.01). At postoperative month 6, VA improved to 0.555 ± 0.405 logMAR (P < 0.05). VA improved by at least 2 lines in 56% and at least 4 lines in 28%. For ARTs, preoperative VA was 1.460 ± 0.391 logMAR. MHD was 390.2 ± 203.7 µm (range, 132-687 µm). All 5 ARTs (100%) resulted in MTMH closure. At postoperative month 6, VA was stable at 1.000 ± 0.246 logMAR (P = 0.08). Visual acuity improved at least 2 lines in 25%. CONCLUSIONS: Surgical closure of macular holes improved VA in 57% of MTMHs. Internal limiting membrane flaps achieved better anatomic and functional outcomes than ILM peeling alone. Autologous retinal transplantation may be an option for refractory MTMHs. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

SURGICAL OUTCOMES OF VASOPROLIFERATIVE RETINAL TUMORS' REFRACTORY TO NONINVASIVE THERAPIES.

PURPOSE: To evaluate the outcomes of surgical treatment of refractory vasoproliferative retinal tumors (VPTs) and its complications. METHODS: Clinical charts of all patients diagnosed with VPTs who underwent surgical treatment from 2005 to 2020 were reviewed. Clinical features, surgical techniques, and outcomes were evaluated. RESULTS: From 25 eyes of 23 patients with VPTs, 17 (68%) eyes underwent surgical intervention to treat tumor activity and associated complications including epiretinal membrane (n = 10, 59%), retinal detachment (n = 8, 47%), and vitreous hemorrhage (n = 3, 18%). All eyes underwent pars plana vitrectomy with endolaser/cryotherapy to control tumor activity and to treat associated complications. Three cases required tumor resection. At the end of follow-up (mean 55.4 months, range 2-305 months), no eye presented tumor activity or retinal detachment after one or two surgeries. There was no epiretinal membrane recurrence. The mean baseline best-corrected visual acuity was 1.2 ± 0.7 logMAR, and the mean final best-corrected visual acuity was 0.7 ± 0.6 logMAR ( P < 0.05). The best-corrected visual acuity improved two or more lines in 12 (70.5%) eyes at the end of follow-up. CONCLUSION: In this series of patients with large active VPTs, surgical intervention allowed control of the tumor activity in all patients and provided overall satisfactory anatomic and functional outcomes.

Subfoveal Choroidal Thickness in Eyes with Neovascular Age-Related Macular Degeneration Treated with Anti-Vascular Endothelial Growth Factor Agents.

PURPOSE: We aimed to assess the subfoveal choroidal thickness (SFChT) and the effect of treatment with anti-vascular endothelial growth factor (anti-VEGF) agents on the SFChT in age-related macular degeneration (AMD) subtypes. METHODS: We enrolled 128 eyes of 107 patients with neovascular AMD (60 women; 47 men; mean age, 73.6 ± 8.9 years), and prospectively evaluated the best-corrected visual acuity (BCVA) and SFChT at baseline and at 3, 6, and 12 months after treatment with anti-VEGF agents. Patients were assigned to the typical AMD, polypoidal choroidal vasculopathy (PCV), and retinal angiomatous proliferation (RAP) subgroups. RESULTS: In total, 85 (66.4%), 31 (24.2%), and 12 (9.4%) eyes were assigned to the typical AMD, PCV, and RAP subgroups, respectively. The baseline mean BCVA was 0.75 ± 0.26, 0.72 ± 0.21, and 0.77 ± 0.24 logMAR in the typical AMD, PCV, and RAP subgroups, respectively (p = 0.774). The mean baseline SFChT was 203.20 ± 35.80, 271.80 ± 24.50, and 182.93 ± 31.31 µm, respectively (p < 0.001). Mean SFChT significantly decreased from baseline to 3, 6, and 12 months after treatment. The RAP subtype presented a significantly higher decrease in SFChT compared to the other subtypes (p = 0.01). The percentage reduction in SFChT was not significantly correlated with the number of injections (r = -0.02; p = 0.823). No association was observed between baseline SFChT and final visual acuity at 12 months (r = 0.0; p = 0.586). CONCLUSIONS: SFChT was greatest in eyes with PCV and least in eyes with RAP. The reduction in SFChT after treatment was greater in the RAP cases. The decrease in SFChT after 12 months of anti-VEGF treatment was not associated with the number of injections and there was no correlation between the baseline SFChT and visual acuity in all AMD subtypes.

Vitreomacular Interface after Anti-Vascular Endothelial Growth Factor Injections in Neovascular Age-Related Macular Degeneration.

PURPOSE: To evaluate the incidence of posterior vitreous detachment (PVD) induced by intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents in cases of neovascular age-related macular degeneration (AMD). DESIGN: Cohort study conducted at a single tertiary referral vitreoretinal practice. PARTICIPANTS: A total of 396 eyes of 295 patients were diagnosed with neovascular AMD between 2009 and 2014. A total of 125 eyes of 112 patients met the inclusion criteria and were evaluated in this study. METHODS: This study included patients with neovascular AMD who presented vitreomacular adhesion (VMA) detected by spectral-domain optical coherence tomography (OCT) at baseline. Eyes with VMA were classified according to the diameter of vitreous attachment to the macular surface measured by OCT, with attachment of ≤1500 µm defined as focal and attachment of >1500 µm defined as broad. All patients received at least 3 monthly intravitreal injections of anti-VEGF agents. Follow-up visits were performed 1 month after each intravitreal injection and included OCT analysis to evaluate the incidence of PVD. MAIN OUTCOME MEASURES: Posterior vitreous detachment induced by anti-VEGF injections. RESULTS: The mean follow-up period was 21.3 months (range, 3-59 months). The mean number of intravitreal injections was 8.3 (range, 3-29 injections). Intravitreal drugs used in the study were ranibizumab (51.5%), bevacizumab (33.5%), and aflibercept (15.0%). Seven eyes (5.6%) developed PVD after intravitreal drug injection (3 eyes after the first intravitreal injection: bevacizumab in 1 and ranibizumab in 2; 2 eyes after the second injection: ranibizumab in 1 and bevacizumab in 1; 1 eye after the fourth injection: ranibizumab; and 1 eye after the sixth injection: aflibercept). A total of 118 eyes remained with persistent VMA. All 7 eyes that developed PVD were classified as having focal VMA, with the diameter of vitreous attachment ranging from 210 to 1146 µm (mean, 600 µm). CONCLUSIONS: Intravitreal injections of commonly used anti-VEGF intravitreal drugs rarely induce PVD in patients with neovascular AMD. Eyes with focal VMA have a greater chance to develop PVD than eyes with a broad area of VMA.

Characteristics of Neovascular Age-Related Macular Degeneration in Brazilian Patients.

PURPOSE: To report features of neovascular age-related macular degeneration (AMD) in Brazilian patients. PROCEDURES: Data were prospectively collected from patients diagnosed with neovascular AMD. Eyes were classified as having typical neovascular AMD, polypoidal choroidal vasculopathy (PCV), or retinal angiomatous proliferation (RAP). RESULTS: In total, 265 eyes of 207 patients of predominantly Caucasian ancestry were included; 166 (62.6%) eyes had typical neovascular AMD, 65 (24.5%) eyes had PCV, and 34 (12.8%) eyes had RAP. RAP demonstrated a higher percentage of bilateral cases (p = 0.015). The mean foveal subfield thickness was significantly lower in eyes with PCV (p < 0.001). Cases with typical neovascular AMD had a higher percentage of predominantly classic and minimally classic lesions on fluorescein angiography (FA; p = 0.005). CONCLUSIONS: In Brazilian patients, PCV and RAP represented 24.5 and 12.8% of neovascular AMD cases. Neovascular AMD subtypes differ in relation to clinical features, mean foveal subfield thickness and FA presentation.

AI-based support for optical coherence tomography in age-related macular degeneration.

Artificial intelligence (AI) has emerged as a transformative technology across various fields, and its applications in the medical domain, particularly in ophthalmology, has gained significant attention. The vast amount of high-resolution image data, such as optical coherence tomography (OCT) images, has been a driving force behind AI growth in this field. Age-related macular degeneration (AMD) is one of the leading causes for blindness in the world, affecting approximately 196 million people worldwide in 2020. Multimodal imaging has been for a long time the gold standard for diagnosing patients with AMD, however, currently treatment and follow-up in routine disease management are mainly driven by OCT imaging. AI-based algorithms have by their precision, reproducibility and speed, the potential to reliably quantify biomarkers, predict disease progression and assist treatment decisions in clinical routine as well as academic studies. This review paper aims to provide a summary of the current state of AI in AMD, focusing on its applications, challenges, and prospects.

Intravitreal bevacizumab for type 2 idiopathic macular telangiectasia.

BACKGROUND/AIMS: The aim of this paper is to report the treatment of type 2 nonproliferative idiopathic macular telangiectasia (IMT) with intravitreal bevacizumab (IVB). METHODS: Retrospective case series of 10 eyes of 5 patients with type 2 IMT. All patients received 3 monthly IVB injections. Visual acuity (VA), fluorescein angiography (FA) and optical coherence tomography (OCT) were performed at baseline and 4 weeks after each injection. RESULTS: Four weeks after the third IVB injection, VA remained stable for all patients. All eyes showed some decrease in fluorescein leakage, and there was a mild decrease in central macular thickness. One year later, VA, OCT and FA findings returned to the baseline levels. CONCLUSION: IVB did not improve VA in cases of type 2 IMT.

Association analysis of CFH and ARMS2 gene polymorphisms in a Brazilian cohort with age-related macular degeneration.

PURPOSE: To investigate the association between the CFH and ARMS2 gene polymorphisms and age-related macular degeneration (AMD) in a Brazilian cohort. METHODS: We examined 163 individuals with AMD and 154 controls recruited at the Department of Ophthalmology of the Universidade Federal de Minas Gerais, at the Instituto da Visão, and at the Centro Especializado em Olhos, in Brazil, between 2007 and 2012. Genotyping for CFH rs1061170 and ARMS2 rs10490924 single-nucleotide polymorphisms was performed. The odds ratios (OR) for all of the studied genotypes (heterozygous and homozygous) of both genes were calculated compared to homozygous ancestral alleles. RESULTS: Homozygosity for the CFH and ARMS2 at-risk allele was 33.3 and 23.6%, respectively, for AMD individuals and 10.3 and 7.1%, respectively, for controls (p < 0.0001). The OR was 7.2 (95% CI 3.6-14.5; p < 0.001) for the CFH at-risk genotype (CC) and 5.5 (95% CI 2.6-11.8; p < 0.0001) for ARMS2 (TT). Subjects homozygous for both polymorphisms had a much higher risk of developing AMD (n = 14 patients, OR 33.3, 95% CI 12.8-86.4). The proportion of ancestry in each group indicated that AMD patients had a higher European (Caucasian) component than controls. CONCLUSION: CFH and ARMS2 polymorphisms were strongly associated with AMD in this Brazilian cohort.

Approved AI-based fluid monitoring to identify morphological and functional treatment outcomes in neovascular age-related macular degeneration in real-world routine (FRB!).

AIM: To predict antivascular endothelial growth factor (VEGF) treatment requirements, visual acuity and morphological outcomes in neovascular age-related macular degeneration (nAMD) using fluid quantification by artificial intelligence (AI) in a real-world cohort. METHODS: Spectral-domain optical coherence tomography data of 158 treatment-naïve patients with nAMD from the Fight Retinal Blindness! registry in Zurich were processed at baseline, and after initial treatment using intravitreal anti-VEGF to predict subsequent 1-year and 4-year outcomes. Intraretinal and subretinal fluid and pigment epithelial detachment volumes were segmented using a deep learning algorithm (Vienna Fluid Monitor, RetInSight, Vienna, Austria). A predictive machine learning model for future treatment requirements and morphological outcomes was built using the computed set of quantitative features. RESULTS: Two hundred and two eyes from 158 patients were evaluated. 107 eyes had a lower median (≤7) and 95 eyes had an upper median (≥8) number of injections in the first year, with a mean accuracy of prediction of 0.77 (95% CI 0.71 to 0.83) area under the curve (AUC). Best-corrected visual acuity at baseline was the most relevant predictive factor determining final visual outcomes after 1 year. Over 4 years, half of the eyes had progressed to macular atrophy (MA) with the model being able to distinguish MA from non-MA eyes with a mean AUC of 0.70 (95% CI 0.61 to 0.79). Prediction for subretinal fibrosis reached an AUC of 0.74 (95% CI 0.63 to 0.81). CONCLUSIONS: The regulatory approved AI-based fluid monitoring allows clinicians to use automated algorithms in prospectively guided patient treatment in AMD. Furthermore, retinal fluid localisation and quantification can predict long-term morphological outcomes.

Vitreomacular interface after anti-VEGF injections in diabetic macular edema.

BACKGROUND: The purpose of this study was to evaluate the incidence of vitreomacular adhesion (VMA) release after anti-VEGF therapy for the treatment of diabetic macular edema (DME) and to evaluate further changes in outcome. METHODS: This was a retrospective study that enrolled 66 eyes of 66 patients with DME who presented with VMA diagnosed by spectral-domain optical coherence tomography (OCT) at baseline. VMA was classified as focal (attachment: ≤ 1500 µm) or broad (attachment: > 1500 µm). All patients received at least three monthly intravitreal injections of an anti-VEGF agent. Follow-up visits were performed 1 month after each injection to evaluate the incidence of VMA release. RESULTS: The mean patient age was 61.4 years (range: 29 to 78 years), and 72.7 % were male. The mean best-corrected visual acuity was 0.62 logMAR, and the mean central retinal thickness (CRT) was 473 µm at baseline. The mean length of follow-up was 18.5 months, and the mean number of injections was 5.8. The intravitreal drugs used were aflibercept (40.9 %), ranibizumab (37.9 %) and bevacizumab (21.2 %). Forty-seven eyes had broad VMA, and 19 had focal VMA. Twenty-two eyes (33.3 %) developed VMA release following a mean of 5.7 injections (range: 3-13). Sixteen eyes (72.7 %) with focal VMA and 6 eyes (27.3 %) with broad VMA at baseline developed VMA release. Twenty-one eyes that developed VMA release showed an improvement in CRT following VMA release (mean: -106 µm; range: 22 to 289 µm). CONCLUSIONS: VMA release occurs in approximately 1/3 of patients with DME following anti-VEGF therapy. Most of them show a short-term decrease in CRT.

Multimodal Imaging and Histopathological Evaluation of Berger's Space.

OBJECTIVE: To demonstrate the multimodal imaging and histopathology of Berger's space. METHODS: We conducted a retrospective in vivo analysis of 4 patients demonstrating Berger's space with intraocular pathological conditions, documented by slit-lamp biomicroscopic photography and, in 2 patients, also by optical coherence tomography (OCT). Additionally, we carried out a retrospective histological study of 7 enucleated eyes with retinoblastoma demonstrating Berger's space. A review of the literature was also performed. RESULTS: Two eyes had slit-lamp photographs. One case showed Berger's space surrounded by vitreous hemorrhage. In the other case, amyloid was trapped within Berger's space. In another 2 eyes that were pseudophakic, Berger's space was visible on anterior segment OCT. One had amyloid trapped in Berger's space that could be seen with OCT. The histological review of the 7 enucleated eyes with advanced retinoblastoma demonstrated the presence of pyknotic cells in Berger's space. CONCLUSIONS: Berger's space is an actual space in pathological conditions and can be an important site of pathology. Additionally, to our knowledge, this is the first time that Berger's space has been documented by anterior segment OCT in a clinical setting.

DAPI diffusion after intravitreal injection of mesenchymal stem cells in the injured retina of rats.

To evaluate DAPI (4',6-diamidino-2-phenylindole) as a nuclear tracer of stem cell migration and incorporation it was observed the pattern of retinal integration and differentiation of mesenchymal stem cells (MSCs) injected into the vitreous cavity of rat eyes with retinal injury. For this purpose adult rat retinas were submitted to laser damage followed by transplantation of DAPI-labeled BM-MSCs grafts and double-labeled DAPI and quantum dot-labeled BM-MSCs. To assess a possible DAPI diffusion as well as the integration and differentiation of DAPI-labeled BM-MSCs in laser-injured retina, host retinas were evaluated 8 weeks after injury/transplantation. It was demonstrated that, 8 weeks after the transplant, most of the retinal cells in all neural retinal presented nuclear DAPI labeling, specifically in the outer nuclear layer (ONL), inner nuclear layer (INL), and ganglion cell layer (GCL). Meanwhile, at this point, most of the double-labeled BM-MSCs (DAPI and quantum dot) remained in the vitreous cavity and no retinal cells presented the quantum dot marker. Based on these evidences we concluded that DAPI diffused to adjacent retinal cells while the nanocrystals remained labeling only the transplanted BM-MSCs. Therefore, DAPI is not a useful marker for stem cells in vivo tracing experiments because the DAPI released from dying cells in moment of the transplant are taken up by host cells in the tissue.

Use of voriconazole in the surgical management of chronic postoperative fungal endophthalmitis.

Management of postoperative mycotic endophthalmitis remains challenging. This study reports successful management of postoperative chronic fungal endophthalmitis with vitrectomy surgery and voriconazole. A retrospective interventional case series of four eyes of four patients with chronic fungal endophthalmitis treated with pars plana vitrectomy and oral and intravitreal voriconazole is described. Pars plana vitrectomy, en bloc capsulectomy, and explantation of the intraocular lens were then performed combined with one to four intravitreal injections of voriconazole and oral voriconazole for up to 5 weeks. Identified fungal species included Aspergillus, Acremonium, Penicillium, and Verticillium. Voriconazole may have affected the clinical and surgical management of fungal endophthalmitis.

The use of anterior segment optical coherence tomography (ASOCT) in demonstrating recurrence of vitreoretinal lymphoma (VRL) in the anterior vitreous.

BACKGROUND: Primary vitreoretinal lymphoma (VRL) is a rare disease with 30-380 new cases in the United States per year. Its insidious process and spread to the central nervous system (CNS) leads to a mean 5-year survival rate from 41.4 to 71%. Medical treatment of VRL has been summarized extensively in the literature and involves intraocular rituximab and methotrexate as first line agents in unilateral VRL, with systemic chemotherapy to be considered in bilateral or CNS-involving disease. In addition, therapeutic "debulking" vitrectomy has been reported in the literature, with some limited success. Despite this, recurrence rate is high and should always be suspected in the setting of new inflammation. Anterior segment optical coherence tomography (ASOCT) has not been previously used to image VRL recurrence in the anterior vitreous. CASE PRESENTATION: A 63-year-old man, with VRL was found to have cells and debris in the anterior vitreous, 10 months after his first vitrectomy, intravitreal rituximab and methotrexate. Since the patient was phakic at the time of initial vitrectomy, the anterior vitreous had not been removed. ASOCT confirmed the findings. Subsequent surgery removed the lens and debris. Both the patient's vision and ASOCT improved. CONCLUSIONS: We suggest that ASOCT of the anterior segment is a useful diagnostic tool to monitor for recurrence of VRL. In biopsy-proven VRL, phakic patients who undergo therapeutic vitrectomy, should also be considered for lens extraction and anterior vitrectomy to limit recurrences.

Angiographic effects of indocyanine green photobleaching by the diode laser.

BACKGROUND AND OBJECTIVE: To investigate the cause of hypofluorescent spots detected by indocyanine green (ICG) videoangiography in areas subjected to ICG-enhanced transpupillary thermotherapy in pigmented rabbits. MATERIALS AND METHODS: In 6 eyes, two similar areas were treated with transpupillary thermotherapy. A standard dose of ICG (0.5 mg/kg) was injected intravenously before treatment of the second area. Red-free photographs without further injection of ICG (first ICG videoangiography) were then performed. The first area was re-irradiated using the same parameters. Red-free photographs and a second ICG videoangiography, still without further injection of ICG, were performed. ICG was then re-injected and a third ICG videoangiography was obtained. Finally, fluorescein angiography was performed. RESULTS: The first ICG videoangiography demonstrated hyperfluorescence of the first area and normofluorescence of the second area. The second ICG videoangiography demonstrated hypofluorescence of the first area. The third ICG videoangiography showed hyperfluorescence of both areas. CONCLUSIONS: Hypofluorescence detected after re-irradiation is probably related to ICG photobleaching.

Transpupillary thermotherapy alone and enhanced by standard doses of indocyanine green in pigmented rabbits.

BACKGROUND AND OBJECTIVE: To evaluate the chorioretinal effects of transpupillary thermotherapy (TTT) and TTT enhanced by standard doses of indocyanine green (ICG) in pigmented rabbits. MATERIALS AND METHODS: In 25 eyes, two retinal areas were irradiated using identical subthreshold diode laser irradiation. The subthreshold diode laser irradiation level was first determined using the other eye. ICG (0.5 mg/kg) was injected before irradiation of the second area. Red-free photographs, fluorescein angiography, and ICG videoangiography were performed after TTT. Specimens were prepared for light microscopy. RESULTS: In 35% of the cases, ICG videoangiography revealed a hypofluorescent spot in the area irradiated after injection of ICG that disappeared after ICG re-injection. None of the areas irradiated before ICG injection were hypofluorescent. Red-free photographs and fluorescein angiography were normal in most cases. Light microscopy demonstrated patent choriocapillaris and choroid in most areas. CONCLUSIONS: Subthreshold TTT, whether enhanced by ICG or not, did not cause significant choroidal or choriocapillaris vascular occlusion. Standard doses of ICG had no significant effect on TTT.