Diagnostic accuracy of nonmydriatic fundus photography for the detection of glaucoma in diabetic patients.

Purpose. To determine the diagnostic accuracy for glaucoma of a set of criteria with nonmydriatic monoscopic fundus photography (NMFP) in diabetics. Methods. Diabetics recruited from a screening program for diabetic retinopathy and diabetic glaucoma patients recruited from our glaucoma unit were included. Any patient with evidence of diabetic retinopathy was excluded. Diabetic patients had to have no visual field defects to be included as controls. Glaucoma patients had to have a glaucomatous field defect in at least one eye to be included. One NMFP was taken per eye for all subjects. These photographs were evaluated by two masked glaucoma specialists for the presence of the following: bilateral cup to disc (C/D) ratio ≥0.6, notching or thinning of the neuroretinal rim, disc hemorrhages, and asymmetry in the C/D ratio between both eyes ≥0.2.This evaluation led to a dichotomous classification: if any of the above criteria was present, the patient was classified as glaucoma. If none were present, the patient was classified as normal. Results. 72 control subjects and 72 glaucoma patients were included. Evaluation of NMFP had a sensitivity of 79.17% and a specificity of 80.56% for specialist 1 and a sensitivity of 72.22% and a specificity of 88.88% for specialist 2 for the detection of glaucoma. The overall accuracy was 79.83% and 80.55%, respectively. Discussion. NMFP evaluation by a glaucoma specialist may be useful for the detection of glaucoma in diabetics.Ministerio de Economía y Competitivida

Safety of lenadogene nolparvovec gene therapy over 5 years in 189 patients with Leber hereditary optic neuropathy

Purpose: Evaluate the safety profile of lenadogene nolparvovec (Lumevoq®) in patients with Leber hereditary optic neuropathy. Design: Pooled analysis of safety data from 5 clinical studies. Methods: A total of 189 patients received single unilateral or bilateral intravitreal injections of a recombinant adeno-associated virus 2 (rAAV2/2) vector encoding the human wild-type ND4 gene. Adverse events (AEs) were collected throughout the studies, up to 5 years. Intraocular inflammation and increased intraocular pressure (IOP) were ocular AEs of special interest. Other assessments included ocular examinations, vector bio-dissemination and systemic immune responses against rAAV2/2. Results: Almost all patients (95.2%) received 9 × 1010 viral genomes and 87.8% had at least 2 years of follow-up. Most patients (75.1%) experienced at least one systemic AE, but systemic treatment-related AEs occurred in 3 patients, none was serious. Intraocular inflammation was reported in 75.6% of lenadogene nolparvovec-treated eyes. Almost all intraocular inflammations occurred in the anterior chamber (58.8%) or in the vitreous (40.3%) and was of mild (90.3%) or moderate (8.8%) intensity; most resolved with topical corticosteroids alone. All IOP increases were mild to moderate in intensity. No AE led to study discontinuation. Bio-dissemination of lenadogene nolparvovec and systemic immune response were limited. The safety profile was comparable for patients treated bilaterally and unilaterally. Conclusions: Lenadogene nolparvovec has a good overall safety profile with excellent systemic tolerability, consistent with limited bio-dissemination. The product is well tolerated, with mostly mild ocular side effects responsive to conventional ophthalmologic treatments

Indirect Comparison of Lenadogene Nolparvovec Gene Therapy Versus Natural History in Patients with Leber Hereditary Optic Neuropathy Carrying the m.11778G\u3eA MT-ND4 Mutation

INTRODUCTION: Lenadogene nolparvovec is a promising novel gene therapy for patients with Leber hereditary optic neuropathy (LHON) carrying the m.11778G\u3eA ND4 mutation (MT-ND4). A previous pooled analysis of phase 3 studies showed an improvement in visual acuity of patients injected with lenadogene nolparvovec compared to natural history. Here, we report updated results by incorporating data from the latest phase 3 trial REFLECT in the pool, increasing the number of treated patients from 76 to 174. METHODS: The visual acuity of 174 MT-ND4-carrying patients with LHON injected in one or both eyes with lenadogene nolparvovec from four pooled phase 3 studies (REVERSE, RESCUE and their long-term extension trial RESTORE; and REFLECT trial) was compared to the spontaneous evolution of an external control group of 208 matched patients from 11 natural history studies. RESULTS: Treated patients showed a clinically relevant and sustained improvement in their visual acuity when compared to natural history. Mean improvement versus natural history was - 0.30 logMAR (+ 15 ETDRS letters equivalent) at last observation (P \u3c 0.01) with a maximal follow-up of 3.9 years after injection. Most treated eyes were on-chart as compared to less than half of natural history eyes at 48 months after vision loss (89.6% versus 48.1%; P \u3c 0.01) and at last observation (76.1% versus 44.4%; P \u3c 0.01). When we adjusted for covariates of interest (gender, age of onset, ethnicity, and duration of follow-up), the estimated mean gain was - 0.43 logMAR (+ 21.5 ETDRS letters equivalent) versus natural history at last observation (P \u3c 0.0001). Treatment effect was consistent across all phase 3 clinical trials. Analyses from REFLECT suggest a larger treatment effect in patients receiving bilateral injection compared to unilateral injection. CONCLUSION: The efficacy of lenadogene nolparvovec in improving visual acuity in MT-ND4 LHON was confirmed in a large cohort of patients, compared to the spontaneous natural history decline. Bilateral injection of gene therapy may offer added benefits over unilateral injection. TRIAL REGISTRATION NUMBERS: NCT02652780 (REVERSE); NCT02652767 (RESCUE); NCT03406104 (RESTORE); NCT03293524 (REFLECT); NCT03295071 (REALITY)

Current Approach in the diagnosis and management of uveitic glaucoma.

Uveitic glaucoma (UG) typically is associated with very high intraocular pressure (IOP) and more intense optic nerve damage than other glaucoma types.This secondary glaucoma requires an early diagnosis and adequate management of both uveitis and glaucoma. It is mandatory to identify the mechanisms of IOP elevation that in many eyes have multiple combined mechanisms. Management of these patients commonly requires an interdisciplinary approach that includes a glaucoma specialist and rheumatologist to control the inflammation and IOP. Glaucoma surgery is required early in these patients due to the high IOP usually present and is less successful than in primary open-angle glaucoma. Recurrent uveitic episodes, multiple mechanism, and the complications associated with uveitis make surgical management of UG challenging. In this review, the management and treatment of UG are updated to clarify the pathogenesis and prevent optic nerve damageMinisterio de Economía y Competitivida

Diagnostic accuracy of nonmydriatic fundus photography for the detection of glaucoma in diabetic patients.

Purpose. To determine the diagnostic accuracy for glaucoma of a set of criteria with nonmydriatic monoscopic fundus photography (NMFP) in diabetics. Methods. Diabetics recruited from a screening program for diabetic retinopathy and diabetic glaucoma patients recruited from our glaucoma unit were included. Any patient with evidence of diabetic retinopathy was excluded. Diabetic patients had to have no visual field defects to be included as controls. Glaucoma patients had to have a glaucomatous field defect in at least one eye to be included. One NMFP was taken per eye for all subjects. These photographs were evaluated by two masked glaucoma specialists for the presence of the following: bilateral cup to disc (C/D) ratio ��.6, notching or thinning of the neuroretinal rim, disc hemorrhages, and asymmetry in the C/D ratio between both eyes ��.2.This evaluation led to a dichotomous classification: if any of the above criteria was present, the patient was classified as glaucoma. If none were present, the patient was classified as normal. Results. 72 control subjects and 72 glaucoma patients were included. Evaluation of NMFP had a sensitivity of 79.17% and a specificity of 80.56% for specialist 1 and a sensitivity of 72.22% and a specificity of 88.88% for specialist 2 for the detection of glaucoma. The overall accuracy was 79.83% and 80.55%, respectively. Discussion. NMFP evaluation by a glaucoma specialist may be useful for the detection of glaucoma in diabetics.Ministerio de Economía y Competitivida

Utility of Bruch membrane opening-based optic nerve head parameters in myopic subjects

Purpose: To evaluate whether the new rim analysis software with spectral-domain optical coherence tomography (SD-OCT) shows advantages over the retinal nerve fiber layer (RNFL) thickness in patients with moderate myopia. Methods: In this prospective cross-sectional study, we studied 65 healthy subjects, 37 with spherical refractive errors in the range of -3 to -6 D (moderate, G1) and 28 with less than -3 D (low/non-myopic, G0). All patients were examined with Heidelberg Spectralis SD-OCT, including Glaucoma Premium Module Edition (GPME) software. With GPME, we analyzed the neuroretinal rim (Bruch membrane opening-minimum rim width [BMO-MRW]) and RNFL. Results: The average age of subjects was 30.2 ± 9.3 years for G0 and 29.9 ± 7.1 years for G1 (p = 0.903). Mean sphere was −0.5 ± 0.3 D (-1.25 to 0 D) G0 and -3.9 ± 0.3 D (-6.00 to -3 D) G1 (p<0.001). The RNFL thickness comparison between G0 and G1 showed a significantly lower thickness in G1 (p = 0.018). The BMO-MRW measurements were similar in both groups (p = 0.331). With the BMO-MRW examination, the number of sectors classified as pathologic per subject in G1 were significantly lower compared to RNFL analysis (p = 0.023). Conclusions: Ring analysis based on BMO-MRW measurements shows a lower rate of false-positives compared to RNFL thickness when studying healthy moderate myopic eyes and it would be advisable to take this into consideration when analyzing these patients

REFLECT Trial: Efficacy and Safety of Bilateral Gene Therapy for Leber Hereditary Optic Neuropathy

Leber Hereditary Optic Neuropathy (LHON) is a blinding orphan disease leading to bilateral vision loss. Lenadogene nolparvovec (rAAV2/2-ND4) is a gene therapy developed for the treatment of LHON caused by a mutation in the ND4 gene

REFLECT Trial: Efficacy and Safety of Bilateral Gene Therapy for Leber Hereditary Optic Neuropathy

Leber Hereditary Optic Neuropathy (LHON) is a blinding orphan disease leading to bilateral vision loss. Lenadogene nolparvovec (rAAV2/2-ND4) is a gene therapy developed for the treatment of LHON caused by a mutation in the ND4 gene

REFLECT Trial: Efficacy and Safety of Bilateral Gene Therapy for Leber Hereditary Optic Neuropathy

Leber Hereditary Optic Neuropathy (LHON) is a blinding orphan disease leading to bilateral vision loss. Lenadogene nolparvovec (rAAV2/2-ND4) is a gene therapy developed for the treatment of LHON caused by a mutation in the ND4 gene