A Review of Neovascular Glaucoma: Etiology, Pathogenesis, Diagnosis, and Treatment.

Neovascular glaucoma (NVG) is a rare, aggressive, blinding secondary glaucoma, which is characterized by neovascularization of the anterior segment of the eye and leading to elevation of the intraocular pressure (IOP). The main etiological factor is retinal ischemia leading to an impaired homeostatic balance between the angiogenic and antiangiogenic factors. High concentrations of vasogenic substances such as vascular endothelial growth factor (VEGF) induce neovascularization of the iris (NVI) and neovascularization of the angle (NVA) that limits the outflow of aqueous humor from the anterior chamber and increases the IOP. NVG clinical, if untreated, progresses from secondary open-angle glaucoma to angle-closure glaucoma, leading to irreversible blindness. It is an urgent ophthalmic condition; early diagnosis and treatment are necessary to preserve vision and prevent eye loss. The management of NVG requires the cooperation of retinal and glaucoma specialists. The treatment of NVG includes both control of the underlying disease and management of IOP. The main goal is the prevention of angle-closure glaucoma by combining panretinal photocoagulation (PRP) and antiangiogenic therapy. The aim of this review is to summarize the current available knowledge about the etiology, pathogenesis, and symptoms of NVG and determine the most effective treatment methods.

Fundus autofluorescence in the evaluation of diabetic macular edema treatment response.

INTRODUCTION: Fundus autofluorescence (FAF) has shown sensitivity in the detection of macular edema. OBJECTIVES: To evaluate indices formed with FAF and retinal anatomical-functional variables in patients with diabetic macular edema (DME) treated with ziv-aflibercept (ziv-AFL). METHODS: Twenty-nine eyes of 15 DME patients who received ziv-AFL intravitreal injections were included in the study. Best-corrected visual acuity (BCVA), contrast sensitivity (CS), optical coherence tomography (OCT) and FAF were evaluated before treatment and at one and two months. OCT variables were central subfield thickness (CST), macular volume (MV) and macular cube average thickness (MCAT). FAF/BCVA, FAF/CS, FAF/CST, FAF/MV and AF/MCAT indices baseline values were obtained. Analysis was performed with Spearman's rank correlation coefficient and linear regression analysis. RESULTS: There was a significant correlation between baseline FAF/BCVA index and BCVA at second month (rs = - 0.78, p = 0.000), between baseline FAF/CS index and BCVA at second month (rs = -0.68, p = 0.0009) and between baseline FAF/CS index and MV at first month of follow-up (rs = 0.64, p = 0.002). CONCLUSIONS: In DME, composite indices with baseline FAF predict variables such as BCVA in the follow-up of patients receiving ziv-AFL.

INTRODUCCIÓN: La autofluorescencia retiniana (AF) ha mostrado sensibilidad en la detección del edema macular. OBJETIVOS: Evaluar índices formados con la AF y variables anatomofuncionales retinianas en pacientes con edema macular diabético (EMD) tratados con ziv-aflibercept (ziv-AFL). MÉTODOS: Fueron incluidos 29 ojos de 15 pacientes con EMD que recibieron inyecciones intravítreas de ziv-AFL. Se evaluó agudeza visual mejor corregida (AVMC), sensibilidad al contraste (SC), tomografía de coherencia óptica (TCO) y AF, antes del tratamiento, así como al primer y segundo mes de iniciado este. Las variables de la TCO fueron grosor foveal central (GFC), volumen macular (VM) y grosor promedio macular (GPM). Se obtuvieron los valores basales de AF/AVMC, AF/SC, AF/GFC, AF/VM y AF/GPM. Se realizó análisis con el coeficiente de correlación de rangos de Spearman y análisis de regresión lineal. RESULTADOS: Hubo una correlación significativa entre el índice AF/AVMC basal y la AVMC en el segundo mes (rs = −0.78, p = 0.000), entre el índice AF/SC basal y la AVMC en el segundo mes (rs = −0.68, p = 0.0009) y entre AF/SC basal y el VM en el primer mes de seguimiento (rs = 0.64, p = 0.002). CONCLUSIONES: En el EMD, los índices compuestos con AF basales predicen variables como AVMC en el seguimiento de pacientes que reciben ziv-AFL.

Partial thickness sclerectomy and intravitreal anti-VEGF therapy for intractable uveal effusion syndrome.

PURPOSE: To report a case series of three patients with intractable uveal effusion syndrome (UES), treated with partial thickness sclerectomy and intravitreal anti-VEGF therapy. METHODS: Three patients with intractable UES were included. All patients underwent intravitreal anti-VEGF therapy to facilitate resolution of uveal effusion. The concentrations of IL-1ß, IL-6, IL-8, IL-10, IL-12p70, TNF and VEGF in aqueous humor were measured. RESULTS: After the last intravitreal injection, all three eyes had total resolution of the chorioretinal detachment or subretinal fluid. One eye experienced improvement in visual acuity. All patients were free from recurrence during the follow-up period. Aqueous IL-6, IL-8 and VEGF concentrations were elevated in all cases. CONCLUSIONS: Our current data provided the evidence that VEGF was increased in eyes with intractable UES and anti-VEGF therapy was effective, suggesting that partial thickness sclerectomy and intravitreal anti-VEGF therapy could be a new choice for intractable UES.

Intravitreal Dexamethasone as a Rescue for Anti-Vascular Endothelial Growth Factor Therapy in Neovascular Age-Related Macular Degeneration with Persistent Disease Activity and High Treatment Demand.

Purpose: To assess the impact of switching to, or adding, an intravitreal dexamethasone implant (Dex; Ozurdex®) in anti-vascular endothelial growth factor (VEGF) therapy on disease stability and treatment intervals in eyes with neovascular age-related macular degeneration (nAMD) and persistent disease activity and high treatment demand. Methods: This retrospective noncomparative multicenter longitudinal case series included pseudophakic eyes with nAMD and persistent retinal fluid despite regular anti-VEGF therapy (ranibizumab or aflibercept) that received at least 1 intravitreal Dex implant. Visual acuity, central retinal thickness (CRT), and intraocular pressure were recorded before, and after, the addition of Dex to anti-VEGF therapy. Results: Sixteen eyes of 16 patients met the inclusion criteria of persistent fluid despite anti-VEGF therapy, under treatment intervals of ≤7 weeks in 14 instances. Patients were 80.9 ± 7.4 years old and had received 25.5 ± 17.4 anti-VEGF injections before Dex over a period of 36.4 ± 21.9 months before switching. The treatment interval increased from 5.5 ± 3.2 weeks between the last anti-VEGF and first Dex injection to 11.7 ± 7.3 weeks thereafter (P = 0.022). CRT remained stable (385.3 ± 152.1, 383.9 ± 129.7, and 458.3 ± 155.2 µm before switching as well as 12 and 24 months after switching; P = 0.78 and P = 0.36, respectively). An insignificant mean short-term early increase in visual acuity was not sustained over time. Conclusions: The addition of Dex resulted in a relevant and sustained increase in treatment intervals, whereas CRT and visual acuity remained stable in these difficult-to-treat eyes. It may be discussed whether inflammation or other steroid-responsive factors play a significant role in cases of nAMD with nonsatisfactory responses to anti-VEGF.

Maintenance of Vision Needed to Drive after Intravitreal Anti-VEGF Therapy in Patients with Neovascular Age-related Macular Degeneration and Diabetic Macular Edema.

OBJECTIVE: To evaluate the association between intravitreal anti-VEGF therapy and visual acuity (VA)/driving vision maintenance over 4 years in patients with neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME). DESIGN: Retrospective, observational, clinical practice cohort study using data from the Vestrum Health database. PARTICIPANTS: Initial diagnosis (January 1, 2014 to June 30, 2019) of nAMD or DME and ≥ 1 year of treatment/follow-up history. The VA analysis required 4 years of treatment/follow-up history. For the driving vision maintenance analysis, patients required Snellen VA of 20/40 or better at baseline and for ≥ 6 months during year 1 after index intravitreal anti-VEGF treatment in the better-seeing eye. METHODS: A loss-of-driving event was the first clinic visit with VA worse than 20/40 sustained for ≥ 6 consecutive months. Kaplan-Meier analyses estimated the probability of maintaining driving vision over 4 years stratified by year-1 injection number. Cox proportional hazard models examined associations between baseline clinical characteristics and year-1 injection frequency and the risk of losing driving vision. MAIN OUTCOME MEASURES: Mean change in VA over time and by baseline VA, driving vision maintenance probability over time and stratified by anti-VEGF injection frequency, and baseline factors predictive of driving vision maintenance. RESULTS: In year 1, the nAMD and DME cohorts gained 8.5 and 9.5 ETDRS letters, respectively. Between years 1 and 4, patients with nAMD and DME lost 6.6 and 2.7 ETDRS letters, respectively. The probability of maintaining driving vision over 4 years was 56% (nAMD) and 72% (DME); among patients who received 1 to 5, 6 to 7, and ≥ 8 anti-VEGF injections in year 1, corresponding probabilities were 50%, 56%, and 65% (nAMD; P < 0.001) and 63%, 72%, and 77% (DME; P < 0.001). Baseline factors associated with driving vision loss included older age, worse index VA, geographic atrophy (nAMD), and worsening baseline diabetic retinopathy (DME). CONCLUSIONS: Older age and worse index VA were risk factors for driving vision loss, whereas a greater year-1 injection number was associated with driving vision maintenance through year 4, supporting early initiation and frequent anti-VEGF injections for maintaining driving vision in nAMD or DME. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Safety and clinical effectiveness of intravitreal administration of bevacizumab (Lumiere®) in patients with neovascular age-related macular degeneration.

The present study was an open-label, prospective, uncontrolled and multicenter clinical trial to investigate the safety and effectiveness of bevacizumab (Lumiere®) administered by the intravitreal route for the treatment of neovascular age-related macular degeneration (nAMD). A total of 22 patients without previous treatment with anti-vascular endothelial growth factor were recruited. Monthly therapy with 1.25 mg intravitreal bevacizumab was applied. Adverse events (AE), visual acuity (VA) and central retinal thickness (CRT) were assessed at baseline, day 1 and day 28 after each injection. A total of 87 AEs were reported; most of them were not serious (96.6%), expected (65.5%) and occurred after the third injection (56.3%). The most frequent AE was 'conjunctival hemorrhage' (29.9% of AEs), attributed to the injection procedure. Treatment was not suspended due to safety reasons in any case. After six months, a statistically significant gain of +8.2 (SD±8.8) letters and a CRT reduction of -75.50 µm (SD±120.3) were achieved with unilateral therapy. VA improvement and CRT reduction were also achieved with bilateral therapy, although to a lesser extent. The results of the present study suggested that therapy with a minimum of 3 doses of bevacizumab over a 6-month period was well tolerated and resulted in a sustained response regarding VA improvement and CRT reduction from the beginning of therapy compared with the baseline value. The study protocol was registered at clinicaltrials.gov (ref. no. NCT03668054).

Choroidal Neovascularization Associated with Punctate Inner Choroidopathy: Combination of Intravitreal Anti-VEGF and Systemic Immunosuppressive Therapy.

PURPOSE: Choroidal neovascularization (CNV) associated with punctate inner choroidopathy (PIC) is a rare clinical entity, yet still a challenge for medical treatment. A case of a young myopic woman developing CNV secondary to unilateral PIC is presented. Clinical morphology, diagnostic procedure and follow-up are reported. CASE REPORT: A 29-year-old woman presented with multiple yellowish dots at the posterior pole. No other signs of inflammation could be seen. Angiography with fluorescein yielded hyperfluorescent signals in the affected areas with a diffuse leak, and SD-OCT showed a slightly elevated retinal pigment epithelial layer, consistent with the diagnosis of PIC. Additionally a classic CNV was observed. RESULTS: Anti-inflammatory therapy with local prednisolone acetate eye drops in combination with intravitreal injection of anti-vascular endothelial growth factor (VEGF, bevacizumab) yielded an increased best-corrected visual acuity. As CNV reappeared, systemic medication with prednisone and azathioprine in combination with two further intravitreal injections of anti-VEGF stabilized CNV and increased visual acuity again. CONCLUSION: Combined therapy of immunosuppression with intravitreal anti-VEGF injections can be considered as therapeutic strategy in the management of recurrent CNV associated with PIC.

Anti-vascular endothelial growth factor therapy for diabetic macular edema.

Diabetes mellitus is a serious health problem that affects over 350 million individuals worldwide. Diabetic retinopathy (DR), which is the most common microvascular complication of diabetes, is the leading cause of new cases of blindness in working-aged adults. Diabetic macular edema (DME) is an advanced, vision-limiting complication of DR that affects nearly 30% of patients who have had diabetes for at least 20 years and is responsible for much of the vision loss due to DR. The historic standard of care for DME has been macular laser photocoagulation, which has been shown to stabilize vision and reduce the rate of further vision loss by 50%; however, macular laser leads to significant vision recovery in only 15% of treated patients. Mechanisms contributing to the microvascular damage in DR and DME include the direct toxic effects of hyperglycemia, sustained alterations in cell signaling pathways, and chronic microvascular inflammation with leukocyte-mediated injury. Chronic retinal microvascular damage results in elevation of intraocular levels of vascular endothelial growth factor A (VEGF), a potent, diffusible, endothelial-specific mitogen that mediates many important physiologic processes, including but not limited to the development and permeability of the vasculature. The identification of VEGF as an important pathophysiologic mediator of DME suggested that anti-VEGF therapy delivered to the eye might lead to improved visual outcomes in this disease. To date, four different inhibitors of VEGF, each administered by intraocular injection, have been tested in prospective, randomized phase II or phase III clinical trials in patients with DME. The results from these trials demonstrate that treatment with anti-VEGF agents results in substantially improved visual and anatomic outcomes compared with laser photocoagulation, and avoid the ocular side effects associated with laser treatment. Thus, anti-VEGF therapy has become the preferred treatment option for the management of DME in many patients.