Recessive MECR pathogenic variants cause an LHON-like optic neuropathy.

BACKGROUND: Leber's hereditary optic neuropathy (LHON) is a mitochondrial disorder characterised by complex I defect leading to sudden degeneration of retinal ganglion cells. Although typically associated with pathogenic variants in mitochondrial DNA, LHON was recently described in patients carrying biallelic variants in nuclear genes DNAJC30, NDUFS2 and MCAT. MCAT is part of mitochondrial fatty acid synthesis (mtFAS), as also MECR, the mitochondrial trans-2-enoyl-CoA reductase. MECR mutations lead to a recessive childhood-onset syndromic disorder with dystonia, optic atrophy and basal ganglia abnormalities. METHODS: We studied through whole exome sequencing two sisters affected by sudden and painless visual loss at young age, with partial recovery and persistent central scotoma. We modelled the candidate variant in yeast and studied mitochondrial dysfunction in yeast and fibroblasts. We tested protein lipoylation and cell response to oxidative stress in yeast. RESULTS: Both sisters carried a homozygous pathogenic variant in MECR (p.Arg258Trp). In yeast, the MECR-R258W mutant showed an impaired oxidative growth, 30% reduction in oxygen consumption rate and 80% decrease in protein levels, pointing to structure destabilisation. Fibroblasts confirmed the reduced amount of MECR protein, but failed to reproduce the OXPHOS defect. Respiratory complexes assembly was normal. Finally, the yeast mutant lacked lipoylation of key metabolic enzymes and was more sensitive to H2O2 treatment. Lipoic Acid supplementation partially rescued the growth defect. CONCLUSION: We report the first family with homozygous MECR variant causing an LHON-like optic neuropathy, which pairs the recent MCAT findings, reinforcing the impairment of mtFAS as novel pathogenic mechanism in LHON.

Peripapillary hyperreflective ovoid mass-like structures (PHOMS) in patients with acute Leber's hereditary optic neuropathy.

PURPOSE: Peripapillary hyperreflective ovoid mass-like structures (PHOMS) represent an optical coherence tomography (OCT) finding that has been characterized in different forms of pseudopapilledema. The aim of this study was to investigate the prevalence of PHOMS in patients affected by acute LHON using structural OCT, and to provide a detailed description of these findings. METHODS: Patients with a clinical and molecularly confirmed diagnosis of acute LHON (visual loss having occurred less than 6 months) were enrolled from the neuro-ophthalmology clinic at San Raffaele Scientific Institute. Patients had a complete ophthalmologic evaluation, including imaging with structural OCT. RESULTS: Our analysis included 16 patients (21 eyes-8 males and 8 females) with acute LHON. Structural OCT exhibited PHOMS in 12 eyes from 9 patients with a prevalence rate of 57.1%. In a subsequent topographical assessment in the peripapillary area, the most common location of PHOMS was the temporal region (12 out of 12 eyes), while the nasal region was affected in 2 eyes (16.7%). Considering the 12 eyes with PHOMS, mean ± SD temporal peripapillary RNFL thickness was 87.5 ± 28.4 microns. The temporal peripapillary RNFL thickness was significantly lower in eyes without PHOMS (63.7 ± 32.2 microns; P = 0.40). At the 12-month follow-up visit, PHOMS disappeared in 10 out of 12 eyes. CONCLUSIONS: Acute LHON eyes have PHOMS which are mainly confined to the temporal peripapillary sector. PHOMS may represent swelled retinal fibers that have herniated or are in stasis.

PREVALENCE AND MORPHOLOGIC BIOMARKERS OF METAMORPHOPSIA IN EYES WITH "RESOLVED" CHRONIC CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To assess relationships between demographics, clinical characteristics, and optical coherence tomography characteristics with persistence of metamorphopsia after resolution of subretinal fluid in eyes with chronic central serous chorioretinopathy. METHODS: One-hundred participants with "resolved" (absence of subretinal fluid) chronic central serous chorioretinopathy were retrospectively analyzed. Patients underwent a complete ophthalmologic evaluation, including assessment of the presence of metamorphopsia. At the study visit, optical coherence tomography scans were reviewed for qualitative and quantitative features. RESULTS: Sixty-six of 100 patients (66.0%) complained of metamorphopsia. Both the foveal and parafoveal ganglion cell complex thicknesses were thinner in central serous chorioretinopathy eyes with metamorphopsia (35.1 ± 10.6 µ m and 82.0 ± 18.1 µ m vs. 40.7 ± 11.8 µ m and 93.1 ± 13.5 µ m, P = 0.030 and P < 0.0001). In the foveal region, the outer plexiform layer and outer nuclear layer thicknesses were thinner in patients with metamorphopsia (24.6 ± 8.5 µ m and 63.1 ± 20.9 µ m vs. 29.1 ± 8.7 and 76.2 ± 18.2 µ m, P = 0.016 and P = 0.005). The ellipsoid zone band was more frequently discontinued in eyes with metamorphopsia (56.1% vs. 35.3%, P = 0.039). Multivariate stepwise linear regression analysis demonstrated that the strongest associations with the presence of metamorphopsia were with parafoveal ganglion cell complex thickness ( P = 0.004), foveal outer nuclear layer thickness ( P = 0.010), and number of previous recurrences of subretinal fluid accumulation ( P = 0.017). The time interval from the last subretinal fluid resolution was not associated with the presence of metamorphopsia. CONCLUSION: In "resolved" central serous chorioretinopathy, clinical aspects (i.e., number of previous recurrences) and structural changes (i.e., ganglion cell complex and outer nuclear layer thinning) are associated with metamorphopsia after subretinal fluid resolution.

Peripapillary vessel density changes in Leber's hereditary optic neuropathy: a new biomarker.

IMPORTANCE: The contribution of the microvascular supply to the pathogenesis of Leber's hereditary optic neuropathy (LHON) is poorly understood. BACKGROUND: We aimed at measuring the peripapillary capillary vessel density (VD) using optical coherence tomography angiography (OCT-A) at different stages of LHON. DESIGN: Prospective, cross-sectional, multicenter, observational study. PARTICIPANTS: Twenty-two LHON patients divided in four groups: unaffected mutation carriers (LHON-u); early sub-acute stage (LHON-e); late sub-acute stage (LHON-l); chronic stage (LHON-ch). METHODS: OCT-A scans centred on the optic disc were obtained by spectral domain OCT system. MAIN OUTCOME MEASURES: VD, retinal nerve fibre layer (RNFL) and ganglion cell-inner plexiform layer (GC-IPL) thickness were compared between groups. RESULTS: Significant VD changes were detected in every sector (P < 0.0001). In LHON-e, the VD was reduced in the temporal sector compared with LHON-u and in the temporal and inferotemporal sectors compared with controls. In LHON-l, VD was reduced in whole, temporal, superotemporal and inferotemporal sectors compared with LHON-u and controls. In LHON-ch, the VD was reduced in all sectors compared to the other groups. An asynchronous pattern emerged in the temporal sector with VD changes occurring earlier than RNFL thickness changes and together with GC-IPL thinning. CONCLUSIONS AND RELEVANCE: Significant peripapillary miscrovascular changes were detected over the different stages of LHON. Studying the vascular network separately from fibres revealed that microvascular changes in the temporal sector preceded the changes of RNFL and mirrored the GC-IPL changes. Measurements of the peripapillary vascular network may become a useful biomarker to monitor the disease process, evaluate therapeutic efficacy and elucidate pathophysiology.

NUTRITIONAL SUPPLEMENTATION IN AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To evaluate the rate of adherence to prescribed nutritional supplementation in patients affected by age-related macular degeneration, in an Italian tertiary referral tertiary center. METHODS: Patients with age-related macular degeneration, age-related eye disease study Categories 3 and 4, were recruited and underwent an 11-item questionnaire. RESULTS: The study included a total of 193 patients meeting the age-related eye disease study nutritional supplementation criteria (174 patients with age-related eye disease study Category 4 and 19 with Category 3). Seventy-seven (40%) were taking oral supplementation, 70 of whom (90%) 1 tablet/day. Oral supplementation was recommended by the personal ophthalmologist in 85 patients (44%), including all those currently receiving it. Eight patients of 85 (9.4%) rejected supplementation despite it being recommended, mostly because they were already taking other medicines. Ninety-four patients (48%) claimed they had not received any information from their ophthalmologist. CONCLUSION: Our data reveal that Italian patients with age-related eye disease study Categories 3 and 4 have a low adherence to nutritional supplementation. In 65% of cases, patients were not adequately informed by their ophthalmologist of the potential benefits of oral supplementation for age-related macular degeneration; indeed, 108 patients (56%) were not even aware such nutritional treatments are available. Ophthalmologists should be aware of the importance of giving advice to persons with age-related macular degeneration regarding the benefits of oral supplements.

Prospective evaluation of morphological and functional changes after repeated intravitreal dexamethasone implant (Ozurdex®) for retinal vein occlusion.

AIMS: To evaluate changes in macular morphology and function after repeated intravitreal dexamethasone implant (Ozurdex®) for macular edema (ME) due to retinal vein occlusion (RVO). METHODS: Consecutive treatment-naïve patients with ME secondary to RVO were treated with Ozurdex and followed up to 12 months to evaluate functional and morphological outcomes by means of best-corrected visual acuity (BCVA) and microperimetry and by enhanced depth imaging optical coherence tomography, respectively. RESULTS: Thirty-five eyes of 35 patients were included for the analysis (26 central RVO, 9 branch RVO). During the 12-month study period, 8 of the 35 eyes (23%) underwent 1 intravitreal dexamethasone implant, 13 of the 35 eyes (37%) underwent 2, and 14 of the 35 eyes (40%) underwent 3 intravitreal dexamethasone implants. At 1 month from the 1st intravitreal dexamethasone implant, the mean BCVA, retinal sensitivity and central macular thickness (CMT) significantly improved compared to the baseline values. At 3 months, the mean BCVA improvement was no more significant, while retinal sensitivity further improved and CMT slightly worsened, remaining, however, significantly better than at baseline. At 12 months, those eyes that had undergone 2 retreatments showed a significant improvement of the mean BCVA, mean retinal sensitivity and CMT compared to the baseline values [0.61 ± 0.29 logarithm of the minimum angle of resolution (LogMAR) vs. 0.82 ± 0.33 LogMAR, p = 0.011; 12.94 ± 4.73 dB vs. 10.75 ± 3.27 dB, p = 0.043, and 321 ± 91 µm vs. 735 ± 169 µm, p = 0.001, respectively]. In those eyes that had undergone only 1 retreatment, a significant improvement was recorded only for the CMT (500 ± 224 µm vs. 695 ± 302 µm, p = 0.044). The mean retreatment interval between the 1st and the 2nd injection was 4.5 ± 1.1 months (range 3-7 months), and between the 2nd and the 3rd injection it was 4.1 ± 1 months (range 3-6 months). CONCLUSIONS: In eyes with ME secondary to RVO, Ozurdex produces functional benefits as early as 1 month after treatment/retreatment. Current optical coherence tomography and microperimetry findings confirm the concept that, in most cases, the optimum retreatment interval should be <6 months from the 1st injection.

Changes in macular function after ozurdex for retinal vein occlusion.

PURPOSE: To investigate changes in macular function after intravitreal dexamethasone implant (Ozurdex) for macular edema (ME) secondary to retinal vein occlusion (RVO). METHODS: Nineteen treatment-naive patients with RVO-related ME were treated with intravitreal Ozurdex and followed up to 6 months to evaluate functional outcomes, by means of best-corrected visual acuity, microperimetry, and multifocal electroretinography, and their correlations with morphological parameters by enhanced depth imaging optical coherence tomography. RESULTS: Nineteen eyes of 19 patients were included for analysis. At 1 month, mean best-corrected visual acuity, retinal sensitivity, and central macular thickness (CMT) improved from 0.50 ± 0.34 LogMAR, 10.51 ± 4.31 dB, and 762 ± 259 µm (baseline) to 0.38 ± 0.34 LogMAR (p = 0.043), 12.28 ± 5.06 dB (p = 0.025), and 385 ± 191 µm (p = 0.001), respectively. At 3 months, improvement of mean retinal sensitivity and CMT was still significant (11.62 ± 5.05 dB [p = 0.047] and 518 ± 251 µm [p = 0.006]). Multifocal electroretinography measurements also showed (nonsignificant) improvement. No significant changes in choroidal thickness were recorded. Improvements recorded during the first 3 months were no longer significant from month 4. At each time point, we found a negative significant correlation between CMT and retinal sensitivity. Interestingly, 7 eyes did not undergo retreatment of less than 6 months; these eyes showed a significantly better baseline retinal sensitivity than eyes requiring retreatment of less than 6 months (12.27 ± 3.52 dB vs. 9.48 ± 4.53 dB [p = 0.038]). CONCLUSIONS: In eyes with ME secondary to RVO, intravitreal dexamethasone implant provides functional benefits as soon as 1 month after treatment. In most cases, the optimum retreatment interval is less than 6 months from first intravitreal Ozurdex. Microperimetry is a very useful tool to characterize macular function. Baseline macular sensitivity may predict the need for early (<6 months) retreatment.

Fluorescein angiography and spectral-domain optical coherence tomography for monitoring anti-VEGF therapy in myopic choroidal neovascularization.

AIM: To evaluate the agreement between fluorescein angiography (FA) and spectral-domain optical coherence tomography (SD-OCT) in detecting myopic choroidal neovascularization (CNV) activity during bevacizumab treatment. METHODS: Thirty-four patients with subfoveal myopic CNV were prospectively enrolled. FA and SD-OCT were performed at baseline and at all planned monthly visits. After the first injection, additional treatments were administered following detection of fluid on SD-OCT and/or leakage on FA. κ-Analysis was performed to examine the agreement between FA and SD-OCT. RESULTS: At baseline, FA and SD-OCT agreed in 26/34 cases (κ=0.23); sensitivity and specificity were 77.4 and 66.7%, respectively. Seven eyes presented leakage on FA with no fluid on SD-OCT, 1 case showed intraretinal fluid on SD-OCT and no leakage on FA. At the 1-month examination, specificity and κ-value improved, and 30/34 cases showed complete concordance. At the 3- and 4-month examinations, a discordance was noted in 6 cases. From the 5-month examination on, a correspondence was achieved in at least 30/34 cases and reached a perfect match in 11 sessions. CONCLUSIONS: Our study confirms the key role of FA in diagnosing myopic CNV. It seems possible there may be a role for SD-OCT in assisting FA to monitor the myopic CNV activity during anti-vascular endothelial growth factor antibody treatment.

Cardiac Wolframinopathies: A Case Report of Myocarditis and a Literature Review of Cardiac Involvement in Wolfram Syndrome 1.

Purpose: Myocarditis is frequently a sporadic disease, but may also occur in the context of genetic disorders which may increase susceptibility to cardiac inflammation. Cardiac involvement in Wolfram syndrome type 1 (WS1) has been scarcely characterized. To our knowledge, no cases of virus-negative myocarditis have been reported in the WS1 pediatric population. Methods: We report the description of a pediatric case of acute myocarditis in the context of WS1, followed by a literature review of cardiovascular involvement associated with wolframin variants, and discuss potential pathophysiological mechanisms and therapeutic options. Results: A young patient with WS1, treated with insulin and liraglutide, was admitted for acute chest pain. Cardiac magnetic resonance and endomyocardial biopsy were performed to confirm the clinical suspicion of myocarditis. While congenital heart diseases and arrhythmias have been described previously in patients with WS1, this is the first description of virus-negative myocarditis. Conclusions: Myocarditis may represent a possible manifestation of cardiovascular involvement in WS1. Cardiovascular screening may be considered in patients with WS1.

Gene therapy for Leber hereditary optic neuropathy.

INTRODUCTION: Leber hereditary optic neuropathy (LHON) is among the most frequent inherited mitochondrial disease, causing a severe visual impairment, mostly in young-adult males. The causative mtDNA variants (the three common are m.11778 G>A/MT-ND4, m.3460 G>A/MT-ND1, and m.14484T>C/MT-ND6) by affecting complex I impair oxidative phosphorylation in retinal ganglion cells, ultimately leading to irreversible cell death and consequent functional loss. The gene therapy based on allotopic expression of a wild-type transgene carried by adeno-associated viral vectors (AVV-based) appears a promising approach in mitochondrial disease and its efficacy has been explored in several large clinical trials. AREAS COVERED: The review work employed basic concepts in mitochondrial diseases, LHON, and gene therapy procedures. Reports from completed trials in LHON (i.e. RESCUE) were reviewed and critically compared. EXPERT OPINION: New challenges, as the improvement of the contralateral untreated eye or the apparently better outcome in patients treated in later stages (6-12 months), were highlighted by the latest gene therapy trials. A better understanding of the pathogenetic mechanisms of the disease together with combined therapy (medical and gene therapy) and optimization in genetic correction approaches could improve the visual outcome of treated eyes.

Sectorial Ganglion Cell Complex Thickness as Biomarker of Vision Outcome in Patients With Dominant Optic Atrophy.

Purpose: Dominant optic atrophy (DOA) is an inherited condition caused by autosomal dominant mutations involving the OPA-1 gene. The aim of this study was to assess the relationship between macular ganglion cell and inner plexiform layer (GC-IPL) thickness obtained from structural optical coherence tomography (OCT) and visual outcomes in DOA patients. Methods: The study recruited 33 patients with confirmed OPA-1 heterozygous mutation and DOA. OCT scans were conducted to measure the GC-IPL thickness. The average and sectorial Early Treatment Diabetic Retinopathy Study (ETDRS) charts (six-sector macular analysis to enhance the topographical analysis) centered on the fovea were considered. Several regression analyses were carried out to investigate the associations between OCT metrics and final best-corrected visual acuity (BCVA) as the dependent variable. Results: The mean BCVA was 0.43 ± 0.37 logMAR, and the average macular GC-IPL thickness was 43.65 ± 12.56 µm. All of the GC-IPL sectors were significantly reduced and correlated with BCVA. The univariate linear regression and the multivariate stepwise regression modeling showed that the strongest association with final BCVA was observed with the internal superior GC-IPL thickness. Dividing patients based on BCVA, we found a specific pattern. Specifically, in patients with BCVA ≤ 0.3 logMAR, the external superior and inferior sectors together with the internal superior were more significant; whereas, for BCVA > 0.3 logMAR, the external superior sector and internal superior sector were more significant. Conclusions: The study identified OCT biomarkers associated with visual outcomes in DOA patients. Moreover, we assessed a specific OCT biomarker for DOA progression, ranging from patients in the early stages of disease with more preserved GC-IPL sectorial thickness to advanced stages with severe thinning.

AFG3L2 and ACO2-Linked Dominant Optic Atrophy: Genotype-Phenotype Characterization Compared to OPA1 Patients.

PURPOSE: Heterozygous mutations in the AFG3L2 gene (encoding a mitochondrial protease indirectly reflecting on OPA1 cleavage) and ACO2 gene (encoding the mitochondrial enzyme aconitase) are associated with isolated forms of Dominant Optic Atrophy (DOA). We aimed at describing their neuro-ophthalmological phenotype as compared with classic OPA1-related DOA. DESIGN: Cross-sectional study. METHODS: The following neuro-ophthalmological parameters were collected: logMAR visual acuity (VA), color vision, mean deviation and foveal threshold at visual fields, average and sectorial retinal nerve fiber layer (RNFL), and ganglion cell layer (GCL) thickness on optical coherence tomography. ACO2 and AFG3L2 patients were compared with an age- and sex-matched group of OPA1 patients with a 1:2 ratio. All eyes were analyzed using a clustered Wilcoxon rank sum test with the Rosner-Glynn-Lee method. RESULTS: A total of 44 eyes from 23 ACO2 patients and 26 eyes from 13 AFG3L2 patients were compared with 143 eyes from 72 OPA1 patients. All cases presented with bilateral temporal-predominant optic atrophy with various degree of visual impairment. Comparison between AFG3L2 and OPA1 failed to reveal any significant difference. ACO2 patients compared to both AFG3L2 and OPA1 presented overall higher values of nasal RNFL thickness (P = .029, P = .023), average thickness (P = .012, P = .0007), and sectorial GCL thickness. These results were confirmed also comparing separately affected and subclinical patients. CONCLUSIONS: Clinically, DOA remains a fairly homogeneous entity despite the growing genetic heterogeneity. ACO2 seems to be associated with an overall better preservation of retinal ganglion cells, probably depending on the different pathogenic mechanism involving mtDNA maintenance, as opposed to AFG3L2, which is involved in OPA1 processing and is virtually indistinguishable from classic OPA1-DOA.

Genetic variants affecting NQO1 protein levels impact the efficacy of idebenone treatment in Leber hereditary optic neuropathy.

Idebenone, the only approved treatment for Leber hereditary optic neuropathy (LHON), promotes recovery of visual function in up to 50% of patients, but we can neither predict nor understand the non-responders. Idebenone is reduced by the cytosolic NAD(P)H oxidoreductase I (NQO1) and directly shuttles electrons to respiratory complex III, bypassing complex I affected in LHON. We show here that two polymorphic variants drastically reduce NQO1 protein levels when homozygous or compound heterozygous. This hampers idebenone reduction. In its oxidized form, idebenone inhibits complex I, decreasing respiratory function in cells. By retrospectively analyzing a large cohort of idebenone-treated LHON patients, classified by their response to therapy, we show that patients with homozygous or compound heterozygous NQO1 variants have the poorest therapy response, particularly if carrying the m.3460G>A/MT-ND1 LHON mutation. These results suggest consideration of patient NQO1 genotype and mitochondrial DNA mutation in the context of idebenone therapy.

Repeated intravitreal dexamethasone implant (Ozurdex®) for retinal vein occlusion.

PURPOSE: To evaluate the effects of repeated intravitreal dexamethasone implant (IDI) (Ozurdex®) in eyes with macular edema (ME) due to retinal vein occlusion (RVO). METHODS: We reviewed the charts of patients with RVO-related ME, who received repeated Ozurdex IDI (0.7 mg) on an 'as-needed' basis. Main outcome measures included changes in best-corrected visual acuity (BCVA), central macular thickness (CMT), retreatment interval, and incidence of side effects. RESULTS: A total of 33 eyes were included for analysis. Retreatment with Ozurdex was judged necessary after 4.7 ± 1.1 months from the first IDI (1st IDI) and 5.1 ± 1.5 months from the second IDI (2nd IDI). Baseline BCVA was 0.65 ± 0.43 logMAR; it significantly improved to 0.50 ± 0.42 logMAR after 1.4 ± 0.7 months from the 1st IDI (peaking efficacy) (p < 0.001) and to 0.48 ± 0.44 logMAR after 1.8 ± 0.8 months from the 2nd IDI (peaking efficacy) (p < 0.001). CMT decreased from 636 ± 217 µm (baseline) to 300 ± 114 µm, 1.4 ± 0.7 months after the 1st IDI (p < 0.001), and to 298 ± 91 µm, 1.8 ± 0.8 months after the 2nd IDI (p < 0.001). A rebound effect was recorded in 7 eyes after the 1st IDI (mean 168 ± 158 µm) and in 4 eyes after the 2nd IDI (mean 215 ± 199 µm). All eyes with a rebound effect improved again after a 2nd intravitreal Ozurdex injection. No serious adverse events were observed; 12 eyes developed a transient IOP increase, and cataracts were extracted in 2 eyes. CONCLUSION: Repeated intravitreal Ozurdex on an 'as-needed' basis, with a retreatment interval <6 months, may produce long-term clinically meaningful benefits in the treatment of ME due to RVO, without other significant side effects than expected after intraocular corticosteroid treatment.

Choroidal vascularity index in hereditary optic neuropathies.

PURPOSE: To assess the choroidal vascularity index (CVI) in patients affected by Leber hereditary optic neuropathy (LHON) compared to patients affected by dominant optic atrophy (DOA) and healthy subjects. METHODS: In this retrospective study, we considered three cohorts: LHON eyes (48), DOA eyes (48) and healthy subjects' eyes (48). All patients underwent a complete ophthalmologic examination, including best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) acquisition. OCT parameters as subfoveal choroidal thickness (Sub-F ChT), mean choroidal thickness (ChT), total choroidal area (TCA), luminal choroidal area (LCA) were calculated. CVI was obtained as the ratio of LCA and TCA. RESULTS: Subfoveal ChT in LHON patients did not show statistically significant differences compared to controls, while in DOA a reduction in choroidal thickness was observed (p = 0.344 and p = 0.045, respectively). Mean ChT was reduced in both LHON and DOA subjects, although this difference reached statistical significance only in DOA (p = 0.365 and p = 0.044, respectively). TCA showed no significant differences among the 3 cohorts (p = 0.832). No changes were detected in LCA among the cohorts (p = 0.389), as well as in the stromal choroidal area (SCA, p = 0.279). The CVI showed no differences among groups (p = 0.898): LHON group was characterized by a similar CVI in comparison to controls (p = 0.911) and DOA group (p = 0.818); the DOA group was characterized by a similar CVI in comparison to controls (p = 1.0). CONCLUSION: CVI is preserved in DOA and LHON patients, suggesting that even in the chronic phase of the neuropathy the choroidal structure is not irreversibly compromised.

Visual Outcomes and Optical Coherence Tomography Biomarkers of Vision Improvement in Patients With Leber Hereditary Optic Neuropathy Treated With Idebenone.

PURPOSE: To assess the relationship of demographics, clinical characteristics and structural optical coherence tomography (OCT) findings to long-term visual outcomes in patients with Leber hereditary optic neuropathy (LHON) treated with idebenone. DESIGN: Retrospective, interventional, noncomparative clinical cohort study. METHODS: In this study, a total of 17 participants (34 eyes) with LHON treated with idebenone therapy within 1 year after disease onset and 2 years (24 months) of regular follow-ups were retrospectively enrolled. At baseline, structural OCT volume scans of the macula and optic nerve were reviewed to measure metrics reflecting neuronal loss (ie, macular ganglion cell and inner plexiform layer [GC-IPL] and peripapillary retinal nerve fiber layer [RNFL] thicknesses). Stepwise multiple regression analyses were computed to assess associations between final best-corrected visual acuity (BCVA) at 2 years and change in BCVA from baseline at 2 years as dependent variables with demographics, clinical characteristics, and OCT metrics at baseline (visit before the initiation of treatment). RESULTS: The BCVA was 1.6±0.8 logMAR (Snellen VA of ∼20/800) at baseline (visit before the initiation of treatment) and 1.0±0.7 logMAR (Snellen VA of 20/200) at the 2-year follow-up visit (P < .0001). Mean±SD change in BCVA from baseline at 2 years was -51.9%±35.9%. In multivariable analysis, the strongest associations with final BCVA were with baseline BCVA (P = .012), superior macular GC-IPL thickness (P = .044), superotemporal macular GC-IPL thickness (P = .010), and inferotemporal macular GC-IPL thickness (P = .015). Similarly, the strongest associations with delta BCVA were with superior macular GC-IPL thickness (P = .045), superotemporal macular GC-IPL thickness (P = .047), and inferotemporal macular GC-IPL thickness (P = .030). CONCLUSION: We identified OCT biomarkers associated with long-term (ie, 2-year) visual outcomes in patients with LHON treated with idebenone therapy in the first year after disease onset. Thinning of the GC-IPL in the superior and temporal parafoveal regions was associated with worse long-term visual outcomes in these patients.