Intravitreal Therapy Research Articles

Thirty-Year Experience of Radiotherapy for Primary Intraocular Lymphoma with and without Chemotherapy.

Primary intraocular lymphoma (PIOL) is a rare presentation of primary central nervous system lymphoma (PCNSL). We previously reported that ocular radiation therapy (RT) is an excellent option that can spare appropriate patients' upfront toxicity of whole brain radiotherapy (WBRT) and aggressive chemotherapy. A decade later, we expanded this series with almost double median follow up time. We identified all patients seen at our institution from 1990-2022 treated for PCNSL or who received RT to the orbits. Detailed chart review was completed for cases with isolated ocular involvement at presentation (PIOL) who received RT to unilateral or bilateral orbits. Patients with disease on MRI brain or CSF cytology were excluded. Analysis included Kaplan-Meier method, log-rank-test, and Wilcoxon rank sum test. Overall survival (OS) was measured from diagnosis. Freedom-from-recurrence (FFR) measured time from RT start to first recurrence identified on imaging (parenchymal), slit-lamp exam (ocular), or biopsy. A total of 75 patients were treated with RT to the orbits as part of management of PCNSL. 29 had PIOL with median follow up of 52 months from diagnosis. Of this subset, 22 (76%) received RT at our institution, median age at diagnosis was 65 (31-84) and 18 (62%) had bilateral disease. The majority were diagnosed by vitrectomy or vitreoretinal biopsy with B-cell lymphoma or unspecified lymphoma and 3 were clinically diagnosed. 17 patients received RT alone, 10 received RT after induction chemotherapy and 2 with induction and consolidation chemotherapy. Younger patients received chemotherapy (median age 60 vs 70, p = 0.03). RT dose ranged from 30 to 45 Gy, and 20 (69%) received 36 Gy, primarily with 1.8 Gy fractions. 22 (76%) received RT to bilateral orbits. 21 (72%) developed recurrence (Table 1), of which 6 (28.5%) recurred in a RT-treated eye and 11 (52.4%) isolated in the brain. 2 got salvage orbital RT and 4 got WBRT. Median OS was 5.4 years (95% CI 3.9, 7.6) and FFR was 8.4 months (95% CI 5.0, 25). There was no difference in OS (p = 0.4) or FFR (p = 0.3) between combined modality therapy versus RT alone. In this updated experience, we demonstrate that RT alone remains an effective option for isolated PIOL, especially for those at risk of poor toleration of chemotherapy. Systemic therapy or WBRT can be utilized at recurrence, which primarily occurs in the brain. Future comparisons are needed to compare orbital RT to intravitreal therapies, and to investigate how these methods can complement each other to further improve management.

Intravitreal Vascular Endothelial Growth Factor Inhibitor Therapy in Denmark and 5-Year Projections

This cohort study examines the use of intravitreal injections of vascular endothelial growth factor inhibitor in Denmark from 2007 through 2022 and forecasts future demand for this therapy.

FROM DRUSEN TO TYPE 3 MACULAR NEOVASCULARIZATION.

To investigate the imaging features preceding the occurrence of type 3 (T3) macular neovascularization (MNV) using tracked spectral-domain optical coherence tomography. From a cohort of eyes with T3 MNV and ≥ 12 months of previously tracked spectral-domain optical coherence tomography, T3 lesions that developed above soft drusen were selected for optical coherence tomography analysis. Retinal imaging findings at the location where type T3 MNV occurred were analyzed at each follow-up until the onset of T3 MNV. The following optical coherence tomography parameters were assessed: drusen size (height and width), outer nuclear layer/Henle fiber layer thickness at the drusen apex, and the presence of intraretinal hyperreflective foci, retinal pigment epithelium disruption, incomplete retinal pigment epithelium and outer retina atrophy, and complete retinal pigment epithelium and outer retina atrophy. From a cohort of 31 eyes with T3 MNV, T3 lesions developed above soft drusen in 20 eyes (64.5%). Drusen showed progressive growth ( P < 0.001) associated with outer nuclear layer/Henle fiber ( P < 0.001) thinning before T3 MNV. The following optical coherence tomography features were identified preceding the occurrence of T3 MNV, typically at the apex of the drusenoid lesion: disruption of the external limiting membrane/ellipsoid zone and/or the retinal pigment epithelium, hyperreflective foci, and incomplete retinal pigment epithelium and outer retina atrophy/complete retinal pigment epithelium and outer retina atrophy. The results demonstrate specific anatomic alterations preceding the occurrence of T3 MNV that most commonly originates above soft drusen. Drusen growth, reduced outer nuclear layer/Henle fiber thickness, and retinal pigment epithelium atrophy at the drusen apex precede the development of T3 MNV. Identifying these optical coherence tomography features should warrant close monitoring for identification of T3 MNV, which can benefit from prompt intravitreal anti-vascular endothelial growth factor therapy.

Cost-utility model of new intravitreous units vs. current patient journey model in Spain

AimTo compare the effectiveness and costs of the implementation of the Intravitreal Therapy Unit Model, endorsed by the SERV, SECA, SEO and SEDISA, compared to the usual procedure. MethodAnalytical decision model that compares an UTI-type healthcare organization with 4 usual practice scenarios in Spain, in terms of quality-of-life results due to loss of visual acuity and the use of resources. The probability, cost, and quality-adjusted life years (QALYs) were estimated for each scenario proposed. A univariate sensitivity analysis was performed for each of the parameters used in the model. ResultThe model showed that from any of the initial scenarios of the usual practice, transitioning to the UTI-type implementation improves the quality of life of patients and requires lower cost. UTI-type is dominant respect usual practice. The sensitivity analysis showed that the results would not change sign with the variation of any starting variable. ConclusionsShorten suspicion-needle times is key to maintaining functional vision in patients requiring intravitreal treatment. The UTI-type model seeks the efficiency of ophthalmology services and can produce savings that vary between Є175 and Є85 per patient attended per year.

Prevalence of geographic atrophy in Nordic countries and number of patients potentially eligible for intravitreal complement inhibitor treatment: A systematic review with meta-analyses and forecasting study.

We systematically reviewed the literature on the prevalence of geographic atrophy (GA) in Nordic populations, conducted meta-analyses on age-stratified estimates, and calculated current and future number of patients and those potentially eligible for intravitreal complement inhibitor treatment. We followed the PRISMA guidelines, and our protocol was registered in PROSPERO. Ten databases were searched on 22 April 2023 for population-based studies of GA prevalence. Based on clinical descriptive analyses of GA and eligibility criteria of the phase III studies for intravitreal pegcetacoplan (complement C3 and C3b inhibitor), we were able to calculate the proportion of patients with GA potentially eligible for therapy. Finally, we extracted population data for Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) from Eurostat, applied prevalence statistics to the extracted census and forecasting data to estimate the number of patients with GA, and then applied the proportion eligible for intravitreal pegcetacoplan therapy. We identified six studies with a total of 10 159 individuals. Prevalence of GA was estimated to 0.4% (95% confidence intervals [CI]: 0.2%-0.8%), 1.5% (95% CI: 0.7%-2.6%), and 7.6% (95% CI: 4.6%-11.3%) for individuals aged 60-69, 70-79, and 80+ years, respectively. In Nordic countries, we estimate a total of 166 307 individuals with GA in 2023, increasing to 277 893 in 2050. Of these, 90 803 individuals in 2023, increasing to 151 730 in 2050, are potentially eligible for intravitreal complement inhibitor treatment. Considering these large numbers, our study highlights the importance of this topic in the coming years and its potential to significantly impact our clinical practice, organization, and staffing.

Análisis coste-utilidad del modelo de unidad de terapia intravítrea (UTI) frente a la administración tradicional de terapia intravítrea

AimTo compare the effectiveness and costs of the implementation of the intravitreal therapy unit model, endorsed by the SERV, SECA, SEO and SEDISA, compared to the usual procedure. MethodAnalytical decision model that compares an UTI-type healthcare organization with four usual practice scenarios in Spain, in terms of quality-of-life results due to loss of visual acuity and the use of resources. The probability, cost, and quality-adjusted life years (QALYs) were estimated for each scenario proposed. A univariate sensitivity analysis was performed for each of the parameters used in the model. ResultThe model showed that from any of the initial scenarios of the usual practice, transitioning to the UTI-type implementation improves the quality of life of patients and requires lower cost. UTI-type is dominant respect usual practice. The sensitivity analysis showed that the results would not change sign with the variation of any starting variable. ConclusionsShorten suspicion-needle times is key to maintaining functional vision in patients requiring intravitreal treatment. The UTI-type model seeks the efficiency of ophthalmology services and can produce savings that vary between €175 and €85 per patient attended per year.

EFFECT OF TOPICAL SODIUM DICLOFENAC AS ADJUVANT TO INTRAVITREAL BEVACIZUMAB INJECTION THERAPY ON VISUAL ACUITY INTRAOCULAR PRESSURE CHANGES IN PATIENTS WITH DIABETIC MACULAR EDEMA

Introduction dan Aim: Diabetic Macular Edema (DME) in Diabetic Retinopathy (DR) patients might threaten the patient's visual acuity. Therefore, a robust DME treatment is needed to prevent sight threatening condition in DR patients. In this study, we intended to compare the effects of intravitreal administration of bevacizumab versus bevacizumab and topical natrium diclofenac in DR patients who developed DME. Methods: This was a randomized controlled trial study with double blinds. Data were taken from April 2020 to June 2021 from the Dr. Sardjito Central General Hospital and the Dr. Suhardi Hardjolukito Indonesian Air Force Central Hospital, Yogyakarta. Our patients were assigned to a control group (intravitreal bevacizumab therapy only) and an intervention group (intravitreal bevacizumab and topical natrium diclofenac). Then, we evaluated best corrected visual acuity (LogMar) and intraocular pressure (IOP, mmHg) were recorded in both groups before and after therapy. Results: A total of 38 eyes from 36 patients with naive DME were included in this study. Both treatment groups showed a statistically significant improvement in visual acuity after treatment bevacizumab (pre = 0.8±0.5; post = 0.6±0.5; p-value = 0.033) and bevacizumab and natrium diclofenac (pre = 0.9±0.5; post = 0.5±0.3; p-value = 0.004). In contrast to the above findings, the IOP in both groups did not show a significant change in IOP after therapy, bevacizumab (pre = 15.7±4.1; post = 15.6±4.2; p-value = 0.810) and bevacizumab and natrium diclofenac (pre = 16.0±4.5; post = 16.0±3.9; p-value = 0.868). Conclusion: Our study showed that visual acuity was improved significantly in DME patients treated with either bevacizumab or bevacizumab and natrium diclofenac. This might be a valuable information on the improvement of DME therapy, given that no increased post-therapy IOP in patients treated topical natrium diclofenac.

Intravitreal Injection of Anti-Vascular Endothelial Growth Factors Combined with Corticosteroids for the Treatment of Macular Edema Secondary to Retinal Vein Occlusion: A Systematic Review and Meta-Analysis

ABSTRACT Purpose To evaluate the efficacy and safety of intravitreal anti-vascular endothelial growth factor (anti-VEGF) and corticosteroid combination therapy for the management of treatment-naïve or recurrent/refractory macular edema caused by retinal vein occlusion (RVO) in comparison with anti-VEGF monotherapy. Methods In this systematic review and meta-analysis study, the data from publications in the electronic databases including PubMed, Embase, Cochrane Library Central Register of Controlled Trials, ISI and Scopus from January 1, 2007, through November 20, 2020, were compiled. Heterogeneity was statistically quantified by the I2 statistic, and meta-analysis was performed using a random-effects model. Results Twenty-four related studies were identified, including a total of 1280 eyes, which consisted of 685 and 507 patients with central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO), respectively. This study demonstrated a greater improvement in best-corrected visual acuity (BCVA) in the combination group compared to anti-VEGF monotherapy for both CRVO and BRVO cases at 6 months after initiating therapy. The improvement in vision was more notable in BRVO cases than in CRVO cases. However, the changes in central macular thickness (CMT) did not differ significantly between the different treatment approaches, and the results were inconclusive. Including all cases with RVO, there was no inferiority in terms of BCVA improvement and CMT reduction in the triamcinolone subgroup compared with the slow-release dexamethasone implant subgroup. A greater improvement was noticed in terms of BCVA in the sequentially treated subgroup compared to the simultaneous treatment subgroup, while there was a greater reduction in CMT in the simultaneous subgroup with the highest reduction recorded at 1 month after treatment. Conclusions This study suggests that combination therapy with intravitreal anti-VEGF and corticosteroid (such as intravitreal or subtenon triamcinolone or dexamethasone implant) has a slightly better effect on improving BCVA in cases with BRVO or CRVO at 6 months compared to monotherapy.

Comparing the Optical Coherence Tomography Outcomes of Intravitreal Injection Anti Vascular Endothelial Growth Factor in Branch Retinal Vein Occlusion (BRVO)

Background: BRVO is a blockage of the branches of the retinal vein due to a thrombus. The prevalence of 10-year BRVO is 1.6 per 100 subjects. The effect of anti-VEGF injection on BRVO management is effective in improving visual acuity and reducing macular oedema.&#x0D; Case presentation: A man, 32 years old, presented to the ophthalmology clinic at the Dr. M. Djamil General Hospital with a chief complaint of blurred vision in his left eye 1 week before admission. The blurred vision began suddenly. Visual acuity in LE was 20/50 and did not advance with a pinhole. Funduscopic examination of LE showed clear media, rounded papillae with well-defined borders, blood vessels aa:vv = 1:3, venous tortuosity (+) increased in the inferotemporal quadrant; retina: Bleeding (+) with dot blot and flame-shaped inferiorly, exudate (+) cotton wool spots at the inferotemporal region; foveal reflex (+)↓ on the macula. OCT LE examination showed macular intraretinal hypo-reflection and macular thickening with a central macular thickness of 617 μm. The physical examination showed a body weight of 114.9 kg, a height of 173 cm, and a body mass index of 38.4. Within 5 months after 3 times administrations of intravitreal injections of anti-VEGF bevacizumab and ranibizumab, visual acuity of LE: 20/25 was obtained, and increased appearance of the retinal fundus and OCT LE.&#x0D; Conclusion: Intravitreal injection therapy of anti-VEGF bevacizumab and ranibizumab is effective in reducing macular oedema and restoring visual acuity in BRVO.

Prediction of Visual Acuity in Pathologic Myopia with Myopic Choroidal Neovascularization Treated with Anti-Vascular Endothelial Growth Factor Using a Deep Neural Network Based on Optical Coherence Tomography Images.

Myopic choroidal neovascularization (mCNV) is a common cause of vision loss in patients with pathological myopia. However, predicting the visual prognosis of patients with mCNV remains challenging. This study aimed to develop an artificial intelligence (AI) model to predict visual acuity (VA) in patients with mCNV. This study included 279 patients with mCNV at baseline; patient data were collected, including optical coherence tomography (OCT) images, VA, and demographic information. Two models were developed: one comprising horizontal/vertical OCT images (H/V cuts) and the second comprising 25 volume scan images. The coefficient of determination (R2) and root mean square error (RMSE) were computed to evaluate the performance of the trained network. The models achieved high performance in predicting VA after 1 (R2 = 0.911, RMSE = 0.151), 2 (R2 = 0.894, RMSE = 0.254), and 3 (R2 = 0.891, RMSE = 0.227) years. Using multiple-volume scanning, OCT images enhanced the performance of the models relative to using only H/V cuts. This study proposes AI models to predict VA in patients with mCNV. The models achieved high performance by incorporating the baseline VA, OCT images, and post-injection data. This model could assist in predicting the visual prognosis and evaluating treatment outcomes in patients with mCNV undergoing intravitreal anti-vascular endothelial growth factor therapy.

Risk of renal damage associated with intravitreal anti-VEGF therapy for diabetic macular edema in routine clinical practice.

Vascular endothelial growth factor inhibitors (anti-VEGF) have been shown to be effective in the treatment of diabetic macular edema. However, there is little information about the systemic effects of intraocular administration of anti-VEGF drugs in patients with coexistent diabetic nephropathy because it can produce adverse renal effects. This retrospective cohort study analyzed the effect of intravitreal anti-VEGF drugs (bevacizumab, ranibizumab, or aflibercept) on eFGR and microalbuminuria (MicA) in patients with diabetic macular edema and nonproliferative retinopathy without chronic kidney disease (CKD). Sixty-six patients were included, 54.5% male and 45.5% female, with a mean age of 66.70 ± 11.6 years. The mean follow-up of patients with antiangiogenic treatment was 42.5 ± 28.07 months, and the mean number of injections was 10.91 ± 7.54. In 12.1% of the cases, there was a worsening of the glomerular filtration rate (eFGR) and a 19.7% worsening of the microalbuminuria (MicA). The number of injections was not related to the worsening of the eFGR (P = 0.74) or the MicA (P = 0.239). No relationship was found between the type of drug and the deterioration of the GFR (P = 0.689) or the MicA (P = 0.53). Based on the results, there is a small proportion of patients with increase in MicA and the decrease in eFGR after anti-VEGF therapy, and these was no associated with the number of injection or the drug type. Ophthalmologists should be aware of renal damage in order to do a close monitoring of renal function and proteinuria after intravitreal administration of anti-VEGF mainly in hypertensive patients.

Prevalence of Geographic Atrophy in Advanced Age-Related Macular Degeneration (AMD) in Daily Practice.

To investigate the prevalence of geographic atrophy (GA) in advanced age-related macular degeneration (AMD) and the proportion of eyes that would meet the indication criteria for treatment with the first intravitreal anti-C3 agent (pegcetacoplan). This retrospective cross-sectional study included all AMD patients who visited the Macular-Retina-Centre Oberkassel in 2021. Eyes were classified according to AMD stages. Eyes with GA were divided into two groups regarding foveal involvement. Baseline factors were compared between eyes with foveal GA (FGA) and eyes with non-foveal GA (NFGA) to identify predictive factors for foveal involvement. A total of 2033 eyes from 1027 patients were included. AMD stage was early in 296 (14.5%) cases, intermediate in 368 (18.1%) cases, and advanced in 1249 (61.4%) cases. A total of 1204 (60%) eyes had GA [932 (77%) FGA and 272 (23%) NFGA], while 125 eyes (27.4% from eyes with advanced dry AMD) met the indication criteria for treatment with intravitreal pegcetacoplan. The proportion of eyes with neovascular AMD was significantly higher in the FGA group compared to the NFGA group [598 (64.2%) vs. 152 (55.8%), p = 0.01]. At least a quarter of eyes with advanced AMD would be suitable for the upcoming intravitreal pegcetacoplan therapy. Foveal involvement of GA in advanced AMD seems to be more likely in neovascular AMD than in dry AMD.

Brolucizumab for recalcitrant macular neovascularization in age-related macular degeneration with pigment epithelial detachment.

To analyze anatomic and functional response to intravitreal brolucizumab in age-related macular degeneration recalcitrant to previous intravitreal anti-VEGF therapies. In this monocentric, one arm, retrospective study, eyes affected by neovascular age-related macular degeneration (nAMD) resistant to other intravitreally injected anti-vascular endothelial growth factor inhibitors were switched to intravitreal brolucizumab. All patients underwent ophthalmological examinations at baseline and in regular follow-up intervals. Best registered visual acuity (BRVA), Goldmann tonometry, intraocular pressure (IOP), central retinal thickness (CRT) and pigment epithelial detachment (PED) characteristics were analyzed at initiation of anti-VEGF treatment, at treatment switch, and at the end of brolucizumab loading phase. The study included 20 eyes of 18 consecutively treated patients (age: 77 ± 6 years). All eyes had macular neovascularization with PED. Previous treatments included intravitreal aflibercept, bevacizumab, and ranibizumab and had not resulted in a significant improvement in BRVA (0.5 ± 0.5 logMAR vs 0.5 ± 0.6 logMAR) or mean CRT (320 ± 60 µm vs 313 ± 83 µm) up to treatment switch to brolucizumab. At the end of the brolucizumab loading phase, there was significant improvement for both BRVA (0.3 ± 0.2 logMAR, P < 0.05) and CRT (264 ± 55 µm, P < 0.05). Under previous anti-VEGF therapy, there was a significant increase/deterioration in both PED area (2.68 mm2 to 5.18 mm2, P < 0.05) and PED volume (0.39 mm3 to 1.07 mm3, P < 0.05); however, both parameters improved after switching to brolucizumab (3.81 mm2 and 0.37 mm3, P < 0.05). Our results suggest a favourable anatomical and visual response after treatment switch to brolucizumab in patients with nAMD refractory to previous anti-VEGF agents.

CAVITARY CHOROIDAL NEVUS SHOWING THICKNESS FLUCTUATIONS IN RESPONSE TO ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY FOR DIABETIC MACULAR EDEMA: A CASE REPORT.

The purpose of this study was to report the multimodal imaging features of a cavitary choroidal nevus showing thickness fluctuations that mirrored the response of diabetic macular edema (DME) to intravitreal antivascular endothelial growth factor (VEGF) therapy. This is a retrospective case report. Multimodal imaging findings including fundus photography, optical coherence tomography (OCT), fluorescein and indocyanine green angiography, OCT-angiography (OCTA), and B-scan ultrasonography were analyzed. A woman in her 80s with a cavitary choroidal nevus and DME was treated with intravitreal anti-VEGF therapy using a pro re nata regimen over 5 years. The choroidal nevus showed thickness fluctuations paralleling the response of DME to anti-VEGF therapy. Worsening of the DME was associated with marked increased choroidal lesion thickness on OCT. Conversely, resolution of DME after intravitreal anti-VEGF injections was followed by choroidal lesion flattening on OCT. Variations of the choroidal lesion thickness were mainly dependent on changes of intralesional hyporeflective caverns on OCT. Our report shows thickness variations of a cavitary choroidal nevus that paralleled the clinical course of DME treated with intravitreal anti-VEGF therapy. To the best of our knowledge, this is the first report on volume variations of a cavitary choroidal nevus after anti-VEGF therapy.

Exploring the Relationship between Anti-VEGF Therapy and Glaucoma: Implications for Management Strategies.

A short-term increase in intraocular pressure (IOP) is a common side effect after intravitreal anti-VEGF therapy, but a sustained increase in IOP with the development of secondary glaucoma has also been reported in some studies after repeated intravitreal anti-VEGF injections. The aim of this review is to present and discuss the possible pathophysiological mechanisms and factors contributing to a sustained rise in IOP, as well as treatment strategies for patients at risk. Close monitoring and adjustable IOP-lowering treatment are recommended for high-risk patients, including those with glaucoma, angle-closure anomalies, ocular hypertension or family history of glaucoma; patients receiving a high number of injections or at shorter intervals; and patients with capsulotomy. Strategies are needed to identify patients at risk in a timely manner and to prevent sustained elevation of IOP.

FUNGAL ENDOPHTHALMITIS MASQUERADING AS SYMPATHETIC OPHTHALMIA.

To describe the ocular pathology of a patient with fungal endophthalmitis with features mimicking sympathetic ophthalmia. Review of medical records and histopathology of a single patient. A 72-year-old man who sustained penetrating injury to the left eye with an agave plant presented to our clinic 16 months after the initial injury. Before presentation, the patient had developed endophthalmitis and had undergone anterior chamber washout, vitrectomy, and intravitreal steroids, antibiotics, antifungals, and anti-vascular endothelial growth factor 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 sparing the choriocapillaris. These findings were initially attributed to sympathetic ophthalmia. The fellow eye did not have any signs of inflammation, and Grocott methenamine silver stain was positive for filamentous fungal elements, leading to a diagnosis of fungal endophthalmitis. Fungal endophthalmitis may develop histopathologic features that are similar to those observed 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.

Comparison of widefield swept-source optical coherence tomographic angiography and fluorescein fundus angiography for detection of retinal neovascularization with diabetic retinopathy

BackgroundTo compare vitreous angiomosaic images (VAMIs), obtained by widefield swept-source optical coherence tomographic angiography (wfSS-OCTA) and the image of fluorescein fundus angiography (FFA) in the identification of retinal neovascularization (NV) in patients with diabetic retinopathy (DR).MethodsIn this prospective observational study, severe non-proliferative diabetic retinopathy (NPDR) or proliferative DR (PDR) patients were included. All patients underwent FFA and wfSS-OCTA. The number of NVs identified by wfSS-OCTA VAMIs using five fixations 12 × 12 mm montage scans and the resembling FFA images were compared.ResultsFifty-three eyes of 29 patients were enrolled. NVs were detected in 25 eyes by using FFA, including 9 NVs of the disc (NVDs) and 72 NVs elsewhere (NVEs), and in 29 eyes by OCTA, including 11 NVDs and 90 NVEs. The detection rate of NV and NVD of OCTA was comparable to that of FFA (p > 0.05), and the level of agreement was excellent (κ = 0.850, κ = 0.754). Using FFA as the gold standard, the sensitivity for detection of NV by OCTA was 100.0%, specificity was 85.7%, the positive-predictive value was 86.2%, and the negative-predictive value was 100.0%. Compared with FFA, OCTA was superior in terms of the number of NVEs identified (p = 0.024). When we excluded images of patients treated with anti-vascular endothelial growth factor (VEGF) intravitreal therapy for < 3 months, OCTA was comparable to FFA in terms of the number of NVEs discovered (p = 0.203), with excellent agreement (intraclass correlation coefficient = 0.941).ConclusionsWfSS-OCTA is an independent non-invasive alternative to FFA for NV discovery, NVD detection, and individual NVE identification, particularly in patients with PDR who have a history of prior treatment with anti-VEGF.

Long-term efficacy and complications of intravitreal anti-vascular endothelial growth factor agents combined with ablative therapies in juvenile Coats disease: a five year follow-up study.

To evaluate the long-term safety and efficacy of adjuvant intravitreal anti-VEGF therapy in juvenile Coats disease. This retrospective, observational study included a total of 62 eyes in 62 pediatric patients with juvenile Coats disease treated with intravitreal anti-VEGF agents followed for a mean of 67.08months (ranged from 60 to 93months). All affected eyes were managed initially with one session of ablative treatment plus adjuvant intravitreal anti-VEGF agent (0.5mg/0.05ml ranibizumab or conbercept). Ablative treatment was repeated if telangiectatic retinal vessels were not completely regressed or recurred. Anti-VEGF therapy was repeated if subretinal fluid or macular edema still existed. Treatments above were repeated every 2 to 3months. We reviewed clinical and photographic records of patients including the demographics, clinical characteristics and interventions. At final visit, all 62 affected eyes had partially or completely disease resolution; none progressed to advanced stage namely neovascular glaucoma or phthisis bulbi, respectively. No ocular or systemic side effects related to intravitreal injections were observed during follow-up. In terms of 42 affected eyes that could cooperate with visual examination, best corrected visual acuity improved in 14 (14/42, 33.3%) eyes, stabled in 25 (25/42, 59.5%) eyes, and worsened in 3 (3/42, 7.1%) eyes. In the field of complications, 22 (22/62, 35.5%) eyes developed cataracts; 33 (33/62, 53.2%) eyes developed vitreoretinal fibrosis, of whom 14 (14/33, 42.4%) eyes in the subgroup of stage 3B developed progressive TRD; 40 (40/62, 64.5%) eyes developed subretinal fibrosis. Multivariate regression analysis showed increased clinical stage may be associated with the development of vitreo- and subretinal fibrosis (adjusted odds ratio:16.77,17.59; 95% CI:4.50-62.53, 3.98-77.86, respectively, all P < 0.001). Adjuvant intravitreal ranibizumab or conbercept combined with ablative therapies may be a long-term safe and effective treatment for juvenile Coats disease.

RISK FACTORS FOR SURGERY OR BLINDNESS IN NEOVASCULAR GLAUCOMA EYES TREATED WITH ANTI-VEGF INJECTIONS BY A RETINA SPECIALIST.

To determine baseline patient characteristics that predict the need for glaucoma surgery or blindness in eyes with neovascular glaucoma (NVG) despite intravitreal antivascular endothelial growth factor therapy. This is a retrospective cohort study of patients with NVG who had not previously received glaucoma surgery and were treated with intravitreal antivascular endothelial growth factor injections at the time of diagnosis, from September 8, 2011, to May 8, 2020, at a large, retina subspecialty practice. Of 301 newly presenting NVG eyes, 31% required glaucoma surgery and 20% progressed to no light perception vision despite treatment. Patients with intraocular pressure >35 mmHg ( P < 0.001), two or more topical glaucoma medications ( P = 0.003), worse than 20/100 vision ( P = 0.024), proliferative diabetic retinopathy ( P = 0.001), eye pain or discomfort ( P = 0.010), and new patient status ( P = 0.015) at the time of NVG diagnosis were at a higher risk of glaucoma surgery or blindness regardless of antivascular endothelial growth factor therapy. The effect of panretinal photocoagulation was not statistically significant in a subgroup analysis of patients without media opacity ( P = 0.199). Several baseline characteristics at the time of presentation to a retina specialist with NVG seem to portend a higher risk of uncontrolled glaucoma despite the use of antivascular endothelial growth factor therapy. Prompt referral of these patients to a glaucoma specialist should be strongly considered.

Potential of TAK-593 ophthalmic emulsion for the treatment of age-related macular degeneration.

Intravitreal injection therapy of anti-VEGF antibody or steroids is the mainstream for patients with age-related macular degeneration (AMD). However, since intravitreal injection is invasive administration, side effects such as endophthalmitis are major problems. In this study, we selected eye drops as a non-invasive treatment method, and aimed to develop eye drops that can deliver TAK-593 (VEGF receptor tyrosine kinase inhibitor) to the posterior segment of the eye.Since TAK-593 is a poorly water-soluble drug, the TAK-593 emulsion was formulated. The solubility of TAK-593 in various oils was measured, and the oil used for the emulsion was selected. Furthermore, viscosity enhancers were added to the emulsion in order to improve the drug delivery into the eye.As viscosity enhancer, xanthan gum was selected based on the properties and the viscosity of the emulsion. The delivery of TAK-593 to the posterior eye was increased by the formulation concentration and the addition of viscosity enhancers.In the laser-induced choroidal neovascularization model, TAK-593 emulsion eye drops showed the same angiogenesis-suppression efficacy as anti-VEGF antibody intravitreal injection. From these results, it was revealed that TAK-593 with an effective drug concentration can be delivered to the posterior eye by non-invasive eye drop administration.