Age-dependent retinal neuroaxonal degeneration in children and adolescents with Leber hereditary optic neuropathy under idebenone therapy.

BACKGROUND: The aim of this study was to investigate the neuroretinal structure of young patients with Leber hereditary optic neuropathy (LHON). METHODS: For this retrospective cross-sectional analysis, the peripapillary retinal nerve fiber layer (pRNFL) thickness and the macular retinal layer volumes were measured by optical coherence tomography. Patients aged 12 years or younger at disease onset were assigned to the childhood-onset (ChO) group and those aged 13-16 years to the early teenage-onset (eTO) group. All patients received treatment with idebenone. The same measurements were repeated in age-matched control groups with healthy subjects. RESULTS: The ChO group included 11 patients (21 eyes) and the eTO group 14 patients (27 eyes). Mean age at onset was 8.6 ± 2.7 years in the ChO group and 14.8 ± 1.0 years in the eTO group. Mean best-corrected visual acuity was 0.65 ± 0.52 logMAR in the ChO group and 1.60 ± 0. 51 logMAR in the eTO group (p < 0.001). Reduced pRNFL was evident in the eTO group compared to the ChO group (46.0 ± 12.7 µm vs. 56.0 ± 14.5 µm, p = 0.015). Additionally, a significantly lower combined ganglion cell and inner plexiform layer volume was found in the eTO compared to the ChO group (0.266 ± 0.0027 mm3 vs. 0.294 ± 0.033 mm3 , p = 0.003). No difference in these parameters was evident between the age-matched control groups. CONCLUSION: Less neuroaxonal tissue degeneration was observed in ChO LHON than in eTO LHON, a finding that may explain the better functional outcome of ChO LHON.

Childhood versus early-teenage onset Leber's hereditary optic neuropathy: visual prognosis and capacity for recovery.

OBJECTIVE: In Leber's hereditary optic neuropathy (LHON) in children and teenagers, the influence of age on visual prognosis has not yet been investigated. METHODS: Patients from the mitoNET registry with LHON onset at age 4-16 years with at least 4 years of follow-up without treatment were included. Visual acuity (VA) at baseline, lowest VA ever recorded (nadir) and VA at end of follow-up were compared between childhood onset (ChO, ≤12 years of age) and early-teenage onset (eTO; 13-16 years). RESULTS: Out of 231 patients with LHON, 19 met the inclusion criteria (8.2%). There were 11 patients in the ChO and 8 patients in the eTO group. Mean age at onset was 8.6 (SD 2.1) years (ChO) and 15.4 (SD 0.7) years (eTO) (p<0.00001). Follow-up was mean 184 (SD 129) months (ChO) and 119 (SD 78) months (eTO) (p=0.22). Baseline VA was similar between both groups in better (p=0.96) and worse eyes (p=0.54). In worse eyes, both groups deteriorated similarly (p=0.79) until nadir and showed similar recovery until end of follow-up (p=0.38). In better eyes, both groups deteriorated similarly (p=0.16) until nadir. From nadir until end of follow-up, better eyes in the ChO group showed a significantly better recovery (-0.35 (SD 0.36) vs -0.01 (SD 0.06) logMAR; p=0.02) than eTO eyes. CONCLUSION: Visual prognosis of LHON in children is much more favourable in cases of childhood onset (≤12 years of age) as compared with teenage onset (13-16 years), mostly due to better recovery from nadir in childhood onset.

Vitamin B12 in Leber hereditary optic neuropathy mutation carriers: a prospective cohort study.

BACKGROUND: Leber hereditary optic neuropathy (LHON) is the most common mitochondrial disorder, frequently resulting in acute or subacute severe bilateral central vision loss. Vitamin B12 deficiency is also a known cause of optic neuropathy through mitochondrial dysfunction. Here we evaluated the prevalence and clinical significance of vitamin B12 deficiency in a large cohort of LHON patients and asymptomatic mutation carriers from a tertiary referral center. METHODS: From the Munich LHON prospective cohort study, participants included all LHON patients and asymptomatic LHON mutation carriers, who were recruited between February 2014 and March 2020 and consented to participate. Neurological, general, and ophthalmological examinations were regularly performed, as were laboratory tests. Vitamin B12 deficiency was diagnosed if serum vitamin B12 was below 201 pg/mL, or if 201-339 pg/mL plus low serum holotranscobalamin or elevated serum methylmalonic acid or elevated total plasma homocysteine. RESULTS: We analyzed 244 subjects, including 147 symptomatic LHON patients (74% males) and 97 asymptomatic mutation carriers (31% males). Median age at study baseline was 34 years (range 5-82 years). The prevalence of vitamin B12 deficiency was higher for LHON mutation carriers than for the general population in all age categories. This was statistically significant for the LHON mutation carriers under 65 years (21% vs. 5-7%, p = 0.002). While vitamin B12 deficiency prevalence was not statistically different between LHON patients and asymptomatic mutation carriers, its clinical correlates, e.g., macrocytosis and polyneuropathy, were more frequent in the subgroup of LHON patients. Excessive alcohol consumption was a significant predictor of vitamin B12 deficiency (p < 0.05). CONCLUSIONS: The high prevalence of vitamin B12 deficiency in LHON mutation carriers, both asymptomatic mutation carriers and LHON patients, highlights the need for regular vitamin B12 screening in this population, in order to ensure early treatment, aiming for better outcomes. Our study is not conclusive regarding vitamin B12 deficiency as determinant for disease conversion in LHON, and further research is warranted to disentangle the role of vitamin B12 in the pathophysiology and prognosis of LHON.

[Basics of Practical Contact Lens Fitting (Part 2: Practical Process of Contact Lens Fitting, Troubleshooting and Case Reports)]. / Grundlagen der praktischen Kontaktlinsenanpassung. Teil 2.

In times of unlimited availability of exchange lenses on the internet and in discount stores, the contact lens has increasingly become a lifestyle but also a disposable product. The targeted marketing of the contact lens as a mass product could only be realized because the fitting and application of the contact lenses are presented as very simple. The numbers of contact lens-induced complications, as well as the fact that the German market in particular has not seen any increase in the number of contact lens wearers in recent years (2015 to 2019), however, speak a different language.How to fit your patient correctly after a detailed explanation of the different types of contact lenses and their areas of application, how to instruct him or her on how to use them correctly and what risks the patient must be informed about is the subject of this 2nd part of "The basics of practical contact lens fitting". It also explains how to avoid complications that can occur when wearing contact lenses and how to advise and care for patients with contact lens intolerances.

[Basics of Practical Contact Lens Fitting (Part 1: Materials, Indications and Differences in Optics Compared to Glasses)]. / Grundlagen der praktischen Kontaktlinsenanpassung. Teil 1.

The great potential of contact lenses for improving vision in all forms of corneal irregularities, e. g. keratoconus, after keratoplasty, after keratitis, is in danger of being forgotten. Especially by the younger generation of ophthalmologists and opticians there is a risk that the skill of fitting contact lenses professionally will be lost. There are many situations in which the practicing ophthalmologist should recognize that the contact lens can be a useful option for the visual rehabilitation of his patient. In this article, we provide a summary of "The basics of practical contact lens fitting". The first part is about materials, fields of application and differences in optics compared to glasses.

Real-World Clinical Experience With Idebenone in the Treatment of Leber Hereditary Optic Neuropathy.

BACKGROUND: Leber hereditary optic neuropathy (LHON) leads to bilateral central vision loss. In a clinical trial setting, idebenone has been shown to be safe and to provide a trend toward improved visual acuity, but long-term evidence of effectiveness in real-world clinical practice is sparse. METHODS: Open-label, multicenter, retrospective, noncontrolled analysis of long-term visual acuity and safety in 111 LHON patients treated with idebenone (900 mg/day) in an expanded access program. Eligible patients had a confirmed mitochondrial DNA mutation and had experienced the onset of symptoms (most recent eye) within 1 year before enrollment. Data on visual acuity and adverse events were collected as per normal clinical practice. Efficacy was assessed as the proportion of patients with either a clinically relevant recovery (CRR) or a clinically relevant stabilization (CRS) of visual acuity. In the case of CRR, time to and magnitude of recovery over the course of time were also assessed. RESULTS: At time of analysis, 87 patients had provided longitudinal efficacy data. Average treatment duration was 25.6 months. CRR was observed in 46.0% of patients. Analysis of treatment effect by duration showed that the proportion of patients with recovery and the magnitude of recovery increased with treatment duration. Average gain in best-corrected visual acuity for responders was 0.72 logarithm of the minimal angle of resolution (logMAR), equivalent to more than 7 lines on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Furthermore, 50% of patients who had a visual acuity below 1.0 logMAR in at least one eye at initiation of treatment successfully maintained their vision below this threshold by last observation. Idebenone was well tolerated, with most adverse events classified as minor. CONCLUSIONS: These data demonstrate the benefit of idebenone treatment in recovering lost vision and maintaining good residual vision in a real-world setting. Together, these findings indicate that idebenone treatment should be initiated early and be maintained more than 24 months to maximize efficacy. Safety results were consistent with the known safety profile of idebenone.

[Basics for the Preparation of an Ophthalmological Expert Assessment]. / Das augenärztliche Gutachten. Teil 1: Grundlagen für die Erstellung eines augenärztlichen Gutachtens.

The position of the ophthalmologist as an unbiased and impartial expert in the field of tension between the client and the patient is a responsible task that should not be underestimated. Since the ophthalmological expert assessment often has far-reaching legal and financial consequences, it is very important that it is both formally correct and of high quality. Unfortunately, it is becoming increasingly common to find that the examinations required for the preparation of an expert opinion are not carried out optimally, that findings are not substantiated or that formalities are not adhered to correctly. This article will therefore explain how to draw up a correct ophthalmological expert assessment that is legally unassailable. This article deals, among other things, with the most important principles that must be considered in every expert assessment, regardless of the type of assessment. It deliberately does not deal with details that have to be considered in the different types of reports. This is then done in planned follow-up articles.

[Basic Principles of Optics]. / Grundlagen der Optik.

As an ophthalmologist, it is very important to know whether limited vision is caused by refractive problems or whether there is another pathology behind it. That's why refraction plays a key role at the beginning of every eye examination. Therefore, it is important to know the basic principles of optics. When fitting spherical and cylindrical lenses, it is interesting to know which properties the respective lenses have. One should also be aware of the optical paths and refraction laws when fitting spectacle lenses and prisms. In addition, when prescribing spectacle lenses, one should consider changes in the distance between corneal apex and spectacle lens and know conversions for the strength of contact lenses. Only if you have a deeper understanding of refraction and correction of refractive errors you will be able to adjust optimal vision aids for more difficult refraction conditions.

[Optical Care in Low Vision Patients]. / Optische Versorgung von Sehbehinderten.

The numbers of low vision patients will steadily increase because of increasing longevity. It is important to be aware of those patients so that visual rehabilitation can be started as soon as possible and needed. Before the adjustment of low vision devices a diagnosis should be confirmed in order to check any therapeutic option and to ensure the best individual rehabilitation. If there is no further therapeutic option left a detailed anamnesis of the problems due to low vision should be made to ensure that every patient gets the optical or electronic device he really needs in his everyday life. The first step of the adjustment is to get the best subjective refraction for the far distance and the magnification needed for reading. Thereafter, the testing of different devices can start. It is important to know the advantages and disadvantages of the different devices. Besides the optical devices a counceling of the best light and of edge filters should be made. For the prescription of the devices certain criteria must be performed. That way it is possible to reach the main target namely to improve the quality of life of our low vision patients.

Characterization of a Leber's hereditary optic neuropathy (LHON) family harboring two primary LHON mutations m.11778G>A and m.14484T>C of the mitochondrial DNA.

Leber's hereditary optic neuropathy (LHON) is an inherited mitochondrial disease that usually leads to acute or subacute bilateral central vision loss. In 95% of cases, LHON is caused by one of three primary mutations of the mitochondrial DNA (mtDNA), m.11778G>A in the MT-ND4 gene, m.14484T>C in the MT-ND6 gene, or m.3460G>A in the MT-ND1 gene. Here we characterize clinically, genetically, and biochemically a LHON family with multiple patients harboring two of these primary LHON mutations, m.11778G>A homoplasmic and m.14484T>C heteroplasmic. The unusually low male-to-female ratio of affected family members is also seen among the other patients previously reported with two primary LHON mutations m.11778G>A and m.14484T>C. While the index patient had very late onset of symptoms at 75years and severe visual loss, her two daughters had both onset in childhood (6 and 9years), with moderate to mild visual loss. A higher degree of heteroplasmy of the m.14484T>C mutation was found to correlate with an earlier age at onset in this family. Ours is the first LHON family harboring two primary LHON mutations where functional studies were performed in several affected family members. A more pronounced bioenergetic defect was found to correlate with an earlier age at onset. The patient with the earliest age at onset had a more significant complex I dysfunction than all controls, including the LHON patient with only the m.11778G>A mutation, suggesting a synergistic effect of the two primary LHON mutations in this patient.

Evaluation of a vision-related utility instrument: the German vision and quality of life index.

PURPOSE: Multi-attribute utility instruments (MAUIs), which contain a descriptive system, including several health dimensions with associated levels of increasing severity, are used commonly to measure utilities. However, the validity of the descriptive systems rarely is examined using modern psychometric theory. Therefore, we evaluated the psychometric properties of the German version of the Vision and Quality of Life Index (VisQol), a six-item vision-related MAUI. METHODS: The German VisQol was self-administered to 340 patients and 280 controls. All subjects underwent a full ophthalmologic examination, including best-corrected visual acuity (VA) testing. The psychometric properties of the VisQoL were assessed using Rasch analysis. RESULTS: The VisQoL's descriptive system did not function in controls. In patients, after collapsing response categories to resolve disordered thresholds and omitting misfitting persons, the measurement properties (i.e., precision, unidimensionality, and targeting) of the German VisQoL were satisfactory. Most person misfit related to unexpected responses to item 4 ("organizing assistance"). Rasch-generated person estimates were not different between age categories, sex, or underlying ocular condition, but decreased significantly with presence of visual impairment in the better eye (LogMAR ≥ 0.5, 1.20 ± 4.62 compared to 3.46 ± 3.52, P < 0.001). CONCLUSIONS: The German VisQoL's descriptive system displayed adequate fit to the Rasch model after removal of a large proportion of patients with poor fit statistics. However, the wording of item four should be revised to reduce respondent confusion and measurement "noise." The scale's descriptive system does not function in a sample of visually unimpaired persons, most likely due to a lack of variance in the measured trait.