Short-term outcomes of treatment switch to faricimab in patients with aflibercept-resistant neovascular age-related macular degeneration.

PURPOSE: To report short-term outcomes of treatment switch to faricimab in real-world patients with aflibercept-resistant neovascular age-related macular degeneration (AMD). METHODS: Single-center, retrospective cohort study with chart-review using electronic injection database, electronic medical records, and optical coherence tomography (OCT) data from May to September 2023. RESULTS: A total of 50 eyes of 46 patients were analyzed. Faricimab treatment led to absence of fluid in 32% of the eyes and a reduction of fluid in 84% of the eyes. There was a statistically significant decrease in central retinal thickness (CRT) and pigment epithelial detachment (PED) height in those that responded to the switch (median difference: - 31 µm, IQR: 55, p < 0.0001 and median difference: - 21 µm, IQR: 36, p < 0.0001, respectively) and a statistically significant increase in CRT (median difference: + 19 µm, IQR: 20, p = 0.0143) and no change in PED height (median difference: + 22 µm, IQR: 64, p = 0.1508) in those that did not. Best-corrected visual acuity (BCVA) showed marginal decrease with low statistical significance. No ocular or systemic safety events were observed. CONCLUSIONS: Our findings suggest that switching to faricimab is generally safe and effective in patients with neovascular AMD who are otherwise difficult to treat and have residual fluid despite frequent injections with aflibercept. We observed a high rate of morphological response to the treatment switch, improvement of anatomical parameters with about one-third of patients having dry macula following a single injection, and a marginal change in BCVA. Sustainability of these results requires further investigation. STUDY REGISTRATION: ClinicalTrials.gov registration number: NCT06124677. Date of registration: 09/11/2023, retrospectively registered.

Endophthalmitis following same-day bilateral anti-VEGF injections: a systematic review.

PURPOSE: To review the risk of endophthalmitis in same-day bilateral anti-VEGF injections. METHODS: We searched 12 literature databases for studies on the risk of endophthalmitis after same-day bilateral intravitreal anti-VEGF injections. Data extraction was made independently by two authors and discussed afterward until reaching consensus. RESULTS: Seventeen studies were included with a total of 138,478 intravitreal anti-VEGF injections (69,239 bilateral injections sessions) given in at least 7579 patients. In total, 33 cases of endophthalmitis had occurred, and no cases were bilateral. The incidence of endophthalmitis ranged from 0 to 0.53% per intravitreal injection across studies. CONCLUSIONS: We suggest that clinicians can consider same-day treatment of both eyes of patients in need of bilateral intravitreal anti-VEGF injection therapy, but larger studies are needed to quantify the exact risk of endophthalmitis.

Systemic adverse events and all-cause mortality following same-session bilateral intravitreal anti-VEGF injections: a systematic review.

PURPOSE: To review the risk of systemic adverse events and all-cause mortality following same-day bilateral anti-VEGF injections. METHODS: Twelve literature databases were searched for studies on same-session bilateral intravitreal anti-VEGF injections. Studies reporting on systemic adverse events and mortality were included. Data extraction was made independently by two authors and discussed afterwards until consensus was reached. RESULTS: Seven studies were included with a total of 13,406 intravitreal anti-VEGF injections (6703 bilateral injections sessions) given to 689 patients. Across all studies, mean age of patients ranged from 55.7 to 82.5 years, and mean follow-up times ranged from 1.3 to 41 months. Six studies reported on systemic adverse events: Two cases of non-fatal cardiac adverse events were reported after 12,964 injections (6482 bilateral injection sessions) in 626 patients. Four studies reported on death: 12 deaths were recorded after 6233 bilateral injection sessions in a total population of 554 subjects. CONCLUSIONS: We suggest that the risk of non-fatal systemic adverse events and death after same-session bilateral anti-VEGF injection is reasonably low, but larger studies with follow-ups of several years are needed to quantify the exact risk. STUDY REGISTRATION: Prospectively registered in PROSPERO, registration ID: CRD42023428254, registration date: 20/05/2023.

Seven-year outcomes following intensive anti-vascular endothelial growth factor therapy in patients with exudative age-related macular degeneration.

BACKGROUND: Anti-vascular endothelial growth factor (VEGF) therapy is currently the most effective therapy of exudative age-related macular degeneration (AMD). The aim of this study was to assess long-term benefits of intensive aflibercept and ranibizumab anti-VEGF therapy in patients with exudative AMD. METHODS: Two clinical trial sites recruited their original subjects for a re-evaluation 7 years after the baseline visit of the phase-3 Vascular Endothelial Growth Factor (VEGF) Trap-Eye: Investigation of Efficacy and Safety in Wet Age-Related Macular Degeneration (VIEW 2) trial. Forty-seven eyes of 47 patients with AMD originally treated with ranibizumab (14 eyes) or aflibercept (33 eyes) were included. RESULTS: Mean number of injections was 17.8 ± 3.0 during participation in the VIEW 2 trial. Fourteen of 47 (30%) eyes were given additional injections with a mean number of 5.7 ± 4.5 after the trial. At a mean follow-up time of 82 ± 5 months best corrected visual acuity (BCVA) remained stable or improved (≤ 10 letters lost) in 55% of patients in the entire study population, in 43% in the ranibizumab group and in 60% in the aflibercept group. In both groups combined mean BCVA was 54 ± 13 letters at baseline, 65 ± 17 letters at the end of the intensive phase and 45 ± 25 letters at the end of follow-up. There was no statistically significant difference in BCVA between the two groups at baseline (p = 0.88) and at the end of follow-up (p = 0.40). Macular atrophy was observed in 96% of eyes, average area was 7.22 ± 6.31 mm2 with no statistically significant difference between groups (p = 0.47). Correlation between BCVA at end-of-follow-up and the area of atrophy was significant (p < 0.001). At the end of follow-up, fluid was detected in 7 of 47 eyes (15%) indicating disease activity. CONCLUSION: Long-term efficacy of aflibercept and ranibizumab was largely consistent. Following a two-year intensive therapy with as-needed regimen, BCVA was maintained or improved in almost half of the patients and in the ranibizumab group and more than half of the patients in the aflibercept group with very few injections. In a remarkable proportion of eyes, BCVA declined severely which underlines the need for long-term follow-ups and may indicate a more prolonged intensive therapy. TRIAL REGISTRATIONS: VIEW 2 study: ClinicalTrials.gov ID: NCT00637377, date of registration: March 18, 2008. Long-term follow-up: IRB nr.: SE RKEB 168/2022, ClinicalTrials.gov ID: NCT05678517, date of registration: December 28, 2022, retrospectively registered.

Diagnostic Accuracy of the Amsler Grid Test for Detecting Neovascular Age-Related Macular Degeneration: A Systematic Review and Meta-analysis.

Importance: Patients with nonneovascular age-related macular degeneration (AMD) are encouraged to use the Amsler grid test for self-assessment to facilitate early diagnosis. The test is widely recommended, suggesting a belief that it signals worsening AMD, warranting its use in home monitoring. Objective: To systematically review studies of the diagnostic test accuracy of the Amsler grid in the diagnosis of neovascular AMD and to perform diagnostic test accuracy meta-analyses. Data Sources: A systematic literature search was conducted in 12 databases for relevant titles from database inception until May 7, 2022. Study Selection: Studies included those with groups defined as having (1) neovascular AMD and (2) either healthy eyes or eyes with nonneovascular AMD. The index test was the Amsler grid. The reference standard was ophthalmic examination. After removal of obviously irrelevant reports, 2 authors (J.B. and M.S.) independently screened the remaining references in full text for potential eligibility. Disagreements were resolved by a third author (Y.S.). Data Extraction and Synthesis: Two authors (J.B. and I.P.) independently extracted all data and evaluated quality and applicability of eligible studies using the Quality Assessment of Diagnostic Accuracy Studies 2. Disagreements were resolved by a third author (Y.S.). Main Outcomes and Measures: Sensitivity and specificity of the Amsler grid for detecting neovascular AMD with comparators being either healthy control participants or patients with nonneovascular AMD. Results: Of 523 records screened, 10 studies were included with a total of 1890 eyes (mean participant age ranging from 62 to 83 years). Sensitivity and specificity to diagnose neovascular AMD were 67% (95% CI, 51%-79%) and 99% (95% CI, 85%-100%), respectively, when comparators were healthy control participants and 71% (95% CI, 60%-80%) and 63% (95% CI, 49%-51%), respectively, when control participants were patients with nonneovascular AMD. Overall, potential sources of bias were low across studies. Conclusions and Relevance: Although the Amsler grid is easy and inexpensive to use for detection of metamorphopsia, its sensitivity may be at levels typically not recommended for monitoring. Coupling this lower sensitivity with only moderate specificity to identify neovascular AMD in a population at risk, these findings suggest that such patients typically should be encouraged to undergo ophthalmic examination regularly, regardless of any results of Amsler grid self-assessment.

The dark side of the Sun: multimodal imaging of a solar retinopathy case / [A Nap sötét oldala: retinopathia solaris esetének multimodális bemutatása]

Solar retinopathy is the photochemical and thermic injury of the retinal photoreceptors and the pigment epithelium caused by ultraviolet (UV) radiation. As a consequence, the most common symptoms are visual acuity deterioration, blurred vision and positive scotoma. Optical coherence tomography (OCT), microperimetry and fluorescein angiography (FLA) are helpful in determining the diagnosis. Authors present an 18-year-old male having central scotomas affecting both eyes who presented at the Department of Ophtalmology of Semmelweis University. OCT scans revealed a localised defect and hyperreflectivity of certain retinal layers and microperimetry examination detected decreased retinal sensitivity consistent with the lesions. After a follow-up of 6 months, the defect of the right eye became more subtle and the one on the left disappeared completely. Microperimetry results correlated with OCT findings. Subjective symptoms on the right eye decreased significantly and they do not affect his daily life anymore, symptoms on the left eye discontinued. Currently, no specific therapy exists for solar retinopathy. Symptoms and defects in favourable cases normalise in 3­6 months which highlights the importance of public health education and prevention. Orv Hetil. 2020; 161(16): 632­636.

Evaluation of lymphatic vessel dilatations by anterior segment swept-source optical coherence tomography: case report.

BACKGROUND: Conjunctival lymphangiectasia is a rare condition presumably caused by the obstruction of lymphatic channels or by an abnormal connection between conjunctival lymphatic and blood vessels. Diagnosis is based on clinical appearance and histology. We report a case of conjunctival lymphangiectasia in which anterior segment optical coherence tomography (OCT) was used to assist the diagnosis and the planning of the biopsy location. CASE PRESENTATION: A 31-year-old woman was referred with repeated episodes of conjunctival "hemorrhages" and chemosis with extended recovery periods over the last months. Other symptoms were dryness, redness, burning sensation and itching. Photo documentation, anterior segment OCT, ultrasound, computer tomography (CT) and magnetic resonance imaging (MRI) of the brain were performed. MRI revealed dilated atypical Virchow-Robin space (VRS). Conjunctival biopsy was taken and the location of the biopsy was selected based on OCT findings. Based on the clinical appearance we suspected the case to be conjunctival lymphangiectasia or lymphangioma. Histology and immunhistochemistry confirmed the diagnosis of conjunctival lymphangiectasia. CONCLUSIONS: Anterior segment OCT is a non-invasive tool, useful in the evaluation of conjunctival lesions and planning surgery.

Stromal Cell-Derived Factor 1 Polymorphism in Retinal Vein Occlusion.

BACKGROUND: Stromal cell-derived factor 1 (SDF1) has crucial role in the regulation of angiogenesis and ocular neovascularisation (NV). The purpose of this study was to evaluate the association between SDF1-3'G(801)A polymorphism and NV complications of retinal vein occlusion (RVO). METHODS: 130 patients with RVO (median age: 69.0, range 35-93 years; male/female- 58/72; 55 patients had central RVO, 75 patients had branch RVO) were enrolled in this study. In the RVO group, 40 (30.8%) patients were diagnosed with NV complications of RVO and 90 (69.2%) patients without NVs. The median follow up period was 40.3 months (range: 18-57 months). The SDF1-3'G(801)A polymorphism was detected by PCR-RFLP. Allelic prevalence was related to reference values obtained in the control group consisted of 125 randomly selected, age and gender matched, unrelated volunteers (median age: 68.0, range 36-95 years; male/female- 53/72). Statistical analysis of the allele and genotype differences between groups (RVO patients vs controls; RVO patients with NV vs RVO patients without NV) was determined by chi-squared test. P value of <0.05 was considered statistically significant. RESULTS: Hardy-Weinberg criteria was fulfilled in all groups. The SDF1-3'G(801)A allele and genotype frequencies of RVO patients were similar to controls (SDF1-3'A allele: 22.3% vs 20.8%; SDF1-3'(801)AA: 5.4% vs 4.8%, SDF1-3'(801)GG: 60.8% vs 63.2%). The frequency of SDF1-3'(801)AA and SDF1-3'(801)GA genotypes, as well as the SDF1-3'(801)A allele frequency were higher in RVO patients with NV versus in patients without NV complication (SDF1-3'(801)AA+AG genotypes: 57.5% vs 31.1%, p = 0.008; SDF1-3'(801)A allele: 35.0% vs 16.7%, p = 0.002) or versus controls (SDF1-3'(801)AA+AG genotypes 57.5% vs 36.8%, p = 0.021; SDF1-3'(801)A allele: 35.0% vs 20.8% p = 0.01). Carrying of SDF1-3'(801)A allele increased the risk of neovascularisation complications of RVO by 2.69 (OR, 95% CI = 1.47-4.93). CONCLUSION: These findings suggest that carrying SDF1-3'(801)A allele plays a role in the development of neovascular complications in retinal vein occlusion.

[Reproducibility of measurements using the IMEA ADR III critical flicker-fusion frequency measuring device]. / Az IMEA ADR III kritikus fúziós frekvenciavizsgáló eszközzel végzett mérések reprodukálhatóságának vizsgálata.

INTRODUCTION: Measurement of central critical flicker-fusion frequency is a common screening test for eye diseases and additionally it can serve as a useful diagnostic test in numerous neurological and internal diseases. The test might also be used for monitoring purposes. AIM: The aim of the authors was to evaluate a digital central critical flicker-fusion frequency measuring device (IMEA ADR III) in 30 young, healthy Hungarian subjects. METHOD: After a general ophthalmological screening examination, monocular central critical flicker-fusion frequency was measured with four colours. Measurements were carried out on two separate days in three sessions under standardized conditions. Intrasession, intersession and intervisit variabilities, differences in central critical flicker-fusion frequency using the four colours and the effect of certain other influencing factors were determined. RESULTS: There were no statistically significant differences between sessions in the mean and standard deviation of the measurement sets. The central critical flicker-fusion frequency threshold for red colour was significantly lower than for other colours, and the threshold for blue colour was significantly lower than for green. There were no significant differences regarding sex, age, iris colour, and smoking indicating that these factors did not influence the central critical flicker-fusion frequency threshold in these subjects. CONCLUSIONS: Measurement results with the device are reliable and reproducible in healthy, young population in separate sessions.

Leber congenital amaurosis: first genotyped Hungarian patients and report of 2 novel mutations in the CRB1 and CEP290 genes.

PURPOSE: To introduce the first Hungarian patients with genetically defined Leber congenital amaurosis (LCA) and to report 2 novel mutations. METHODS: Seven otherwise healthy patients (4-29 years, 5 male and 2 female) who had an onset of severe visual impairment before age 2 years were investigated. The diagnosis was established in all individuals by medical history, funduscopy, and full-field electroretinogram (ERG). Ocular examination included visual acuity testing, digital fundus photography, and in 6 patients retinal imaging with optical coherence tomography (OCT). Arrayed primer extension microarray screening was performed in all probands. In 2 patients, further Sanger sequencing and targeted next-generation sequencing revealed the second disease allele. RESULTS: A cone-rod type LCA was revealed in 4 patients and a rod-cone type disease in 3 patients. Five patients presented with maculopathy. Optical coherence tomography (OCT) imaging showed diffuse retinal thickening in 3 probands with severe macular atrophy in one. Full-field ERGs were undetectable or residual in all patients. Genetic screening revealed AIPL1, CRB1, and CEP290 gene-related pathology in 6 patients; in 1 proband, no mutation was found. Three homozygous and 3 compound heterozygous mutations were identified. Two novel variants were detected: c.2536G>T (p.G846X) in the CRB1 gene and c.4929delA (p.Lys1643fsX2) in the CEP290 gene. CONCLUSIONS: Genetic subtypes identified are among the most common ones in LCA; the phenotypes are consistent with those reported previously. Both novel mutations are predicted to result in a premature translation termination. The phenotype related to the novel CRB1 mutation results in severe atrophic maculopathy.

Bilateral cystoid macular edema following docetaxel chemotherapy in a patient with retinitis pigmentosa: a case report.

BACKGROUND: Docetaxel is a chemotherapeutic agent of the taxane class of drugs for the treatment of breast cancer. We present a female patient who noted decreased vision after docetaxel treatment. CASE PRESENTATION: A 45-year-old female patient received docetaxel treatment after resection of a breast carcinoma. Funduscopy and optical coherence tomography (OCT) showed cystoid macular edema on both eyes. Dilated funduscopy also showed bone spicule-like pigmented deposits, typical for retinitis pigmentosa. Besides the fundus appearance restricted peripheral vision and scotopic electroretinogram confirmed the diagnosis of retinitis pigmentosa. Chemotherapy was discontinued following a consulation with the oncologist of the patient. After five weeks, visual acuity improved significantly along with decrease of retinal thickness measured by OCT. CONCLUSION: Docetaxel may cause ocular adverse effects such as cystoid macular edema. Ophthalmological examination is warranted for patients with visual complaints during docetaxel chemotherapy.

Optical coherence tomography features of POEMS syndrome and Castleman disease-associated papillopathy.

PURPOSE: To report ocular symptoms and optical coherence tomography (OCT) features of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. METHODS: Case report of two Caucasian patients with POEMS, one of whom also had multicentric Castleman disease. RESULTS: Both patients presented with edema on both optic disks, bilateral macular edema was seen in case 1, and peripapillary choroidal neovascularization was seen on the right side in case 2. OCT confirmed papilledema involving all retinal layers, with additional bilateral peripapillary serous retinal detachment involving the macula in both cases, and peripapillary CNV in case 2. Changes in retinal nerve fiber layer thickness, total peripapillary retinal thickness, and macular detachment were followed with OCT over the course of the disease and after administration of systemic therapy. CONCLUSION: OCT examination of the optic nerve head and the macula has an important additional role in the diagnosis and follow-up of POEMS syndrome and Castleman disease.

Boundary detection errors on optical coherence tomography images in patients with diabetic retinopathy.

BACKGROUND AND OBJECTIVE: To study the incidence of boundary detection errors produced by optical coherence tomography measurements in patients with diabetic retinopathy. PATIENTS AND METHODS: One hundred sixteen eyes with diabetic retinopathy of 64 consecutive patients with diabetes mellitus were included in this retrospective study. The StratusOCT instrument (Carl Zeiss Meditec, Dublin, CA) with the macular thickness map protocol was used for the examinations. After data acquisition, each scan was analyzed using the retinal thickness (single eye) protocol to evaluate whether there was any misdetection of the retinal boundaries. RESULTS: Boundary detection errors were found in 35.3% of eyes. The majority of artifacts were those caused by hard exudates (41.5%), followed by cystoid macular edema (31.7%) and proliferation (17.0%). CONCLUSION: Occurrence of artifacts with optical coherence tomography measurements in cases of diabetic retinopathy is not a rare phenomenon and verification of quantitative measurements is strongly recommended.

A systematic correlation of angiography and high-resolution optical coherence tomography in diabetic macular edema.

PURPOSE: To correlate leakage patterns in fluorescein angiography (FA) images and retinal morphologic features in high-definition optical coherence tomography (HD OCT) images in diabetic macular edema. DESIGN: Prospective pilot study and case series. PARTICIPANTS: Nine consecutive patients (10 eyes) with diabetic macular edema. METHODS: All patients were examined using FA (HRA 2; Heidelberg Engineering) and HD OCT (Carl Zeiss Meditec; resolution, 512x128 pixels, 5.8x5.8 mm, and high-resolution scans consisting of 4096 A scans) on the same day. Using Adobe Photoshop (CS2 Version 9.0; Adobe Systems Incorporated, San Jose, CA) a grid containing 15x7 fields was superimposed on the HD OCT en face image and a late-phase FA image according to retinal landmarks. In each patient, a standardized analysis of 105 subfields was performed to provide a characterization of the type of vascular leakage in FA and the associated retinal morphologic changes in corresponding locations. MAIN OUTCOME MEASURES: Angiographic leakage type and structural alteration in retinal morphologic features in OCT. RESULTS: There was a high consistency between FA and OCT in the petaloid pattern of hyperfluorescence that correlated with the presence of large cystic spaces in the outer nuclear layer (ONL) and the outer plexiform layer (OPL) with or without subretinal fluid in 30.4% and 69.6% of graded fields, respectively. A honeycomblike pattern of hyperfluorescence was associated with swelling and cystic spaces in ONL, OPL, the inner nuclear, and the inner plexiform layer in 71.4% of graded fields. Diffuse patterns of hyperfluorescence did not correlate with characteristic retinal changes in HD OCT, but rather showed diversity in the type of morphologic alteration. The presence of central fluid pooling, such as subretinal fluid, could be identified only by HD OCT and not by FA. CONCLUSIONS: In the examined patients, a petaloid pattern and a honeycomb pattern of hyperfluorescence observed in FA were found to correlate to characteristic changes in HD OCT, whereas a diffuse leakage pattern was associated with nonuniform changes in retinal morphologic features. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.