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.

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.

Vancomycin-associated hemorrhagic occlusive retinal vasculitis masquerading as central retinal vein occlusion / Vasculite hemorrágica oclusiva da retina associada à vancomicina (HORV) mascarada como oclusão da veia central da retina

ABSTRACT A 69-year-old female was referred with sudden unilateral painless decreased vision that began 2 days after uncomplicated cataract surgery in the left eye. Visual acuity was hand motion and biomicroscopy showed a mild anterior chamber reaction, no hypopyon, and an intraocular lens that had been placed within the capsular bag. A dilated fundus examination revealed optic disk edema, widespread deep and superficial intraretinal hemorrhages, retinal ischemia, and macular edema. A cardiological evaluation was normal and thrombophilia tests were negative. After surgery, prophylactic vancomycin (1mg/0.1ml) had been injected intracamerally. The patient was diagnosed with hemorrhagic occlusive retinal vasculitis likely secondary to vancomycin hypersensitivity. Recognition of this entity is important to ensure early treatment and the use of intracameral vancomycin in the fellow eye should be avoided after cataract surgery.

RESUMO Esse caso se refere a uma paciente de 69 anos, sexo feminino, com relato de baixa acuidade visual súbita e indolor no olho esquerdo, de início 2 dias após cirurgia de catarata sem complicações. A acuidade visual era de movimento de mãos e a biomicroscopia mostrou reação de câmara anterior moderada, sem hipópio, e lente intraocular posicionada dentro do saco capsular. A fundoscopia evidenciou edema de disco óptico, hemorragias difusas intrarretinianas superficiais e profundas, isquemia retiniana e edema macular. A avaliação cardiológica foi normal e os testes para trombofilia foram negativos. Ao final da cirurgia foi injetado antibioticoprofilaxia com vancomicina (1mg/0,1ml) na câmara anterior. A paciente foi diagnosticada com vasculite hemorrágica oclusiva da retina secundária à hipersensibilidade a vancomicina. O reconhecimento dessa entidade é importante para o tratamento precoce e para evitar o uso de vancomicina intracameral em caso de cirurgia de catarata no olho contralateral.

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.

Vancomycin-associated hemorrhagic occlusive retinal vasculitis masquerading as central retinal vein occlusion.

A 69-year-old female was referred with sudden unilateral painless decreased vision that began 2 days after uncomplicated cataract surgery in the left eye. Visual acuity was hand motion and biomicroscopy showed a mild anterior chamber reaction, no hypopyon, and an intraocular lens that had been placed within the capsular bag. A dilated fundus examination revealed optic disk edema, widespread deep and superficial intraretinal hemorrhages, retinal ischemia, and macular edema. A cardiological evaluation was normal and thrombophilia tests were negative. After surgery, prophylactic vancomycin (1mg/0.1ml) had been injected intracamerally. The patient was diagnosed with hemorrhagic occlusive retinal vasculitis likely secondary to vancomycin hypersensitivity. Recognition of this entity is important to ensure early treatment and the use of intracameral vancomycin in the fellow eye should be avoided after cataract surgery.

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.

Decisive role of histopathology of lens capsule in the diagnosis of chronic fungal postoperative endophthalmitis.

We report three cases of refractory chronic endophthalmitis after cataract surgery presenting to a referral center, and with repeated negative cultures. Initial treatment consisted of intravitreal and systemic antibiotics, with partial improvement. After subsequent worsening, pars plana vitrectomy, intraocular lens explantation and en bloc capsulectomy were performed. Histopathological examination revealed multiple filamentous fungal structures, sequestered between anterior/posterior lens capsule in all cases. Chronic postoperative fungal endophthalmitis may manifest with negative cultures possibly associated with sequestration of the microorganism into the capsular bag. Careful histopathological examination of lens capsule in these cases may be essential for a definite diagnosis.

Humanistic and Economic Burden of Blindness Associated with Retinal Disorders in a Brazilian Sample: A Cross-Sectional Study.

INTRODUCTION: Vision impairment and blindness have been significantly associated with high medical care expenditures, decrease in health utility, and loss or reduction of productivity. The objective of this study was to assess the humanistic and economic burden of blindness in a Brazilian sample from a societal perspective. METHODS: Cross-sectional, observational, and multicenter study enrolling individuals with blindness (defined as the best corrected visual acuity less than 6/60 in the better-seeing eye) caused by retinal disorders. Data collection was performed between December 2012 and December 2014 through face-to-face interview using a structured questionnaire and three standardized patient-reported outcomes instruments. Direct costs were estimated by multiplying the amount of resources used (12-month recall period) by the corresponding unit cost. Productivity losses were measured using the human capital method. All data were collected in Brazilian real (BRL) and converted to United States dollar (USD), using the exchange rate of 1 USD = 3.0415 BRL (May 7, 2015). RESULTS: A total of 146 subjects from 17 research sites were included with a mean age of 68 (SD = 14.8) years and equal gender distribution. Blindness negatively affected both general and vision-specific health-related quality of life. One-half of patients presented some level of anxiety and depression; of these, about 50% with moderate or severe symptoms. Around one-third of subjects (34.2%) reported at least one fall in the previous 12 months due to vision impairment; of these subjects, 14% reported fractures. Emergency room visits and hospitalization were reported by around 25% and 5% of subjects, respectively. The short-term costs (annual costs) of severe vision impairment or blindness for the studied subjects was USD 128,389.09 (USD 879.37 per person). Total medical direct costs summed USD 116,182.00 (USD 795.77 per person), 61.7% of which was due to outpatient visits (with physicians and other healthcare professionals). The long-term costs (lifetime productivity loss) totalized USD 1,962,599.50 (USD 13,442.47 per person). CONCLUSION: This study demonstrated that blindness imposes both humanistic and economic burden for individuals and for Brazilian society. It also pointed out that there is room to improve blindness management, especially for the poorest people, including health education for individuals, availability of services, and reduction of barriers to patients' access to healthcare assistance. This was a good starting point; however, further research is needed.

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.

Human Stem Cell-Derived Retinal Pigment Epithelial Cells as a Model for Drug Screening and Pre-Clinical Assays Compared to ARPE-19 Cell Line.

BACKGROUND AND OBJECTIVES: Eye diseases have a high socioeconomic impact on society and may be one of the fields in which most stem cell-related scientific accomplishments have been achieved recently. In this context, human Pluripotent Stem Cell (hPSC) technology arises as an important tool to produce and study human Embryonic Stem cell derived-Retinal Pigmented Epithelial Cells (hES-RPE) for several applications, such as cell therapy, disease modeling, and drug screening. The use of this technology in pre-clinical phases attends to the overall population desire for animal-free product development. Here, we aimed to compare hES-RPE cells with ARPE-19, one of the most commonly used retinal pigmented epithelial immortalized cell lines. METHODS AND RESULTS: Functional, cellular and molecular data obtained suggest that hES-RPE cells more closely resembles native RPEs compared to ARPE-19. Furthermore, hES-RPE revealed an interesting robustness when cultured on human Bruch's membrane explants and after exposure to Cyclosporine (CSA), Sirolimus (SRL), Tacrolimus (TAC), Leflunomide (LEF) and Teriflunomide (TER). On these conditions, hES-RPE cells were able to survive at higher drug concentrations, while ARPE-19 cell line was more susceptible to cell death. CONCLUSIONS: Therefore, hES-RPEs seem to have the ability to incur a broader range of RPE functions than ARPE-19 and should be more thoroughly explored for drug screening.

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.

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.

Ocular alterations, molecular findings, and three novel pathological mutations in a series of NF2 patients.

PURPOSE: To evaluate ophthalmological and molecular findings in eight patients with a clinical diagnosis of neurofibromatosis type 2 (NF2). New pathological mutations are described and variability in the ophthalmic phenotype and NF2 allelic heterogeneity are discussed. METHODS: Eye examination was performed in eight NF2 patients, and it included the measurement of the visual acuity, biomicroscopy, dilated fundus examination, color fundus photography, infrared photography, and spectral domain optical coherence tomography (SD-OCT). Molecular analysis was performed with whole-exome sequencing using DNA derived from peripheral blood mononuclear cells from each individual. RESULTS: Ophthalmological features were present in all patients, ranging from subtle retinal alterations identified only using SD-OCT to severe ocular damage present at birth. Six mutations were observed: two patients with stop codon mutation as shown on table 1 and result section, three patients with frameshift mutation as shown on table 1 and result section. Three novel mutations were found among them. CONCLUSIONS: It is a descriptive study of a rare disease, with poor previous literature. Clinical and genetic data are shown, reviving the need to further studies to clarify the genotype-phenotype correlations in NF2.

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.

Quantitative analysis of external limiting membrane, ellipsoid zone and interdigitation zone defects in patients with macular holes.

PURPOSE: To investigate the correlation between the length of external limiting membrane (ELM), ellipsoid zone (EZ) and interdigitation zone (IZ) defects and visual prognosis in patients undergoing macular hole (MH) surgery, using spectral-domain optical coherence tomography (SD-OCT). METHODS: This is a retrospective, consecutive, observational case series study. Fifty-two eyes of 52 patients with primary MH were evaluated. A quantitative analysis of ELM, EZ and IZ defects was performed preoperatively and at 3 and 6 months postoperatively using SD-OCT. The correlation between pre- and postoperative ELM, EZ and IZ defects and the best-corrected visual acuity (BCVA) was investigated. RESULTS: The lengths of ELM, EZ and IZ defects correlated significantly with BCVA in each study period (P < 0.001). Preoperative measures of these band defects were also associated with visual outcomes 3 and 6 months after surgery (P < 0.05). Considering all preoperative parameters, the length of the ELM defect was the factor most strongly correlated with BCVA at 6 months (ß = 0.643, P < 0.012). The integrity of the ELM was the only factor significantly associated with BCVA at 6 months (ß = 0.427; P = 0.004). CONCLUSIONS: The preoperative length of the ELM defect is the strongest predictor of visual acuity after MH surgery. Postoperative integrity of the ELM is significantly associated with visual restoration after surgical treatment of MH.

Influence of Vitreomacular Adhesion on Anti-Vascular Endothelial Growth Factor Treatment for Neovascular Age-Related Macular Degeneration.

PURPOSE: To investigate the effect of vitreomacular adhesion (VMA) on the outcome of antiangiogenic treatment for neovascular age-related macular degeneration (AMD). METHODS: Ninety-nine eyes of 83 patients were used in our cohort study. We prospectively evaluated best corrected visual acuity (BCVA) and central retinal thickness (CRT) in patients with neovascular AMD at baseline and 1, 2, 3, 6, and 12 months after treatment with anti-vascular endothelial growth factor (anti-VEGF) agents. All patients were stratified by spectral domain optical coherence tomography into 2 groups (i.e., VMA[+] and VMA[-]) according to the presence or absence of VMA, and the response to treatment was evaluated. RESULTS: Fifty-four eyes (54.5%) were included in the VMA(-) group and 45 eyes (45.5%) comprised the VMA(+) group. In paired comparisons of mean BCVA between baseline and each follow-up visit (1, 2, 3, 6, and 12 months), the VMA(-) group showed statistically significant improvement at 1, 2, and 3 months compared to baseline, and BCVA significantly improved only at 3 months in the VMA(+) group. For both groups, paired comparisons of CRT showed a statistically significant decrease when data obtained at 1, 2, 3, 6, and 12 months were compared to baseline values (p < 0.05). CONCLUSIONS: Posterior VMA is associated with a worse short-term outcome in patients with neovascular AMD treated with anti-VEGF agents.