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Advances in Therapy Dec 2019Leber's hereditary optic neuropathy (LHON) is a relatively common, rapidly progressing inherited optic neuropathy wherein LHON-affected eyes undergo optic nerve atrophy...
Leber's hereditary optic neuropathy (LHON) is a relatively common, rapidly progressing inherited optic neuropathy wherein LHON-affected eyes undergo optic nerve atrophy due to retinal ganglion cell (RGC) loss. It is a maternally inherited (or sporadic) mitochondrial disorder caused primarily by mutations in genes that encode components of respiratory complex (RC)1 in mitochondria. Mitochondrial deficiency of RC1 compromises ATP production and oxidative stress management in RGCs. The most common LHON-causing mutations are 11778G>A, 3460G>A, and 14484T>C point mutations in MT-ND4, MT-ND1, and MT-ND6. The unusually high mitochondrial load of RGCs makes them particularly sensitive to these mutations. Patients with LHON may be prescribed ubiquinone (a component of RC3) or idebenone, a ubiquinone analogue with enhanced bioavailability to act downstream of RC1. The challenge of accessing the inner mitochondrial membrane with gene therapy for LHON, and other mitochondrial diseases, may be overcome by incorporation of a specific mitochondrion-targeting sequence (MTS) that enables allotropic expression of a nucleus-transcribed ND4 transgene. Because LHON penetrance is incomplete among carriers of the aforementioned mutations, identification of environmental factors, such as heavy smoking, that interact with genetics in the phenotypic expression of LHON may be helpful toward preventing or delaying disease development. LHON has become a model for mitochondrial and neurogenerative diseases owing to it having a clearly identified genetic cause and its early onset and rapid progression characteristics. Hence, LHON studies and genetic treatment advances may inform research of other diseases.
Topics: DNA, Mitochondrial; Electron Transport Complex I; Genetic Therapy; Humans; Mutation; Optic Atrophy, Hereditary, Leber; Phenotype; Point Mutation
PubMed: 31605306
DOI: 10.1007/s12325-019-01113-2 -
Journal of Neurology Feb 2023Since multiple sclerosis (MS) is characterized by an unpredictable disease course, accurate prognosis and personalized treatment constitute an important challenge in...
Since multiple sclerosis (MS) is characterized by an unpredictable disease course, accurate prognosis and personalized treatment constitute an important challenge in clinical practice. We performed a qualitative systematic review to assess the predictive value of retinal layer measurement by spectral-domain optical coherence tomography (SD-OCT) in MS patients. Longitudinal MS cohort studies that determined the risk of clinical deterioration based on peripapillary retinal nerve fiber layer (pRNFL) and/or macular ganglion cell-inner plexiform layer (mGCIPL) atrophy were included. Our search strategy and selection process yielded eight articles in total. Of those, five studies only focused on patients with a relapsing-remitting disease pattern (RRMS). After correction for confounders such as disease duration, we found that (1) cross-sectional measurement of pRNFL thickness ≤ 88 µm; (2) cross-sectional measurement of mGCIPL thickness < 77 µm; (3) longitudinal measurement of pRNFL thinning > 1.5 µm/year; and (4) longitudinal measurement of mGCIPL thinning ≥ 1.0 µm/year is associated with an increased risk for disability progression in subsequent years. Longitudinal mGCIPL assessment consistently resulted in the highest risk estimates in our analysis. Within these studies, inclusion and exclusion criteria accounted for the retinal degeneration inherent to (acute) optic neuritis (ON). This small systematic review provides additional evidence that OCT-measured pRNFL and/or mGCIPL atrophy can predict disability progression in RRMS patients. We therefore recommend close clinical follow-up or initiation/change of treatment in RRMS patients with increased risk for clinical deterioration based on retinal layer thresholds, in particular when other poor prognostic signs co-occur.
Topics: Humans; Prognosis; Tomography, Optical Coherence; Clinical Deterioration; Cross-Sectional Studies; Multiple Sclerosis; Retinal Degeneration; Macular Degeneration; Atrophy
PubMed: 36372866
DOI: 10.1007/s00415-022-11474-4 -
The British Journal of Ophthalmology Nov 2019Compared with current imaging methods, the diagnostic performance and the advantages and limitations of optical coherence tomography angiography (OCTA) remain unclear.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Compared with current imaging methods, the diagnostic performance and the advantages and limitations of optical coherence tomography angiography (OCTA) remain unclear. We performed a systematic review and meta-analysis of studies investigating vessel density (VD) in patients with glaucoma using OCTA.
METHODS
We conducted a literature search on PubMed, Scopus, Web of Science, ISI Conference Proceedings and Google Scholar, along with a manual search, from January 2006 to March 2018. We included prospective studies that used OCTA to compare the VD in glaucomatous eyes with healthy control eyes.
RESULTS
Of 3045 screened articles, 24 were included in a broad characterisation and 18 in the meta-analysis. We observed a statistically significant reduction in the mean peripapillary VD (MPVD) in glaucoma (MPVD: 57.53%, 95% CI 52.60 to 62.46, p< 0.001) compared with controls (MPVD: 65.47%, 95% CI 59.82 to 71.11; standardised mean difference [SMD], -1.41, 95% CI -1.62 to -1.20, p< 0.001) for 888 glaucomatous and 475 healthy eyes, and also in the mean-whole optic nerve image VD (SMD, -9.63, 95% CI -10.22 to -9.03, p<0.001), mean inside-disc VD (SMD, - 9.51, 95% CI -12.66 to -6.36, p<0.05) and mean parafoveal VD (SMD, -3.92, 95% CI -4.73 to -3.12, p<0.001). Subgroup analyses revealed a significant difference in the MPVD across glaucoma subtypes and OCTA devices.
CONCLUSION
This suggests the diagnostic utility of OCTA in detecting glaucomatous eyes; however, further longitudinal prospective studies are welcomed to characterise vascular changes in glaucoma.
Topics: Female; Fluorescein Angiography; Glaucoma, Angle-Closure; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Low Tension Glaucoma; Male; Nerve Fibers; Optic Disk; Prospective Studies; Retinal Ganglion Cells; Tomography, Optical Coherence
PubMed: 30728123
DOI: 10.1136/bjophthalmol-2018-313461 -
Cutaneous and Ocular Toxicology Jun 2022To examine the effects of systemic isotretinoin treatment on the eye using several ocular examination parameters. (Meta-Analysis)
Meta-Analysis
PURPOSE
To examine the effects of systemic isotretinoin treatment on the eye using several ocular examination parameters.
METHODS
We conducted a systemic review for literature published up to June 2021 in both PubMed and Web of Science databases. We included prospective observational or interventional studies evaluating ocular manifestations of isotretinoin in acne patients. The primary outcome measures were anaesthetized and non-anaesthetized Schirmer test, tear break-up time (TBUT), central corneal thickness (CCT), average retinal nerve fibre layer (RNFL) thickness, ganglion cell-inner plexiform layer (GC-IP) thickness, subfoveal choroidal thickness, axial length, ocular surface disease index (OSDI), meibomian gland expression (MGE) and conjunctival stain. The National Institute of Health (NIH) quality assessment tools were used to assess the data quality. The effect size used to analyse the included studies was the weighted mean difference (WMD) and its related confidence intervals (95%CIs).
RESULTS
Twenty-one publications involving 1105 eyes of 842 participants met the inclusion criteria. Isotretinoin use was significantly associated with reduction in the scores of anaesthetized Schirmer (WMD = -2.23, 95%CI: -3.28 to -1.18), non-anaesthetized Schirmer (WMD = -3.74, 95%CI: -4.23 to -3.25), TBUT (WMD = -3.47, 95%CI: -5.09 to -1.86), and CCT (WMD= -7.39, 95%CI: -13.91 to -0.88). Isotretinoin use was significantly associated with increase of OSDI (WMD = 18.29, 95%CI: 7.54-29.03), MGE (WMD = 1.02, 95%CI: 0.70-1.33) and conjunctival stain scores (WMD = 0.61, 95%CI: 0.47-0.76). No significant change was noted in RNFL thickness (WMD = -0.64, 95%CI: -1.80 to 0.51); GC-IP thickness (WMD = 0.42, 95%CI: -1.08 to 1.92); subfoveal choroidal thickness (WMD = -1.80, 95%CI: -6.69 to 3.09), and axial length (WMD = 0.08, 95%CI: -0.19 to 0.35). A significant heterogeneity was found between the study estimates in each of anaesthetized Schirmer, TBUT, MGE, OSDI, and conjunctival stain tests.
CONCLUSION
Isotretinoin use results in a statistically significant reduction of the central corneal thickness, TBUT, and Schirmer test scores. A statistically significant increase in MGE, OSDI and conjunctival stain scores was found. No statistically significant change of average RNFL, GC-IP thickness, subfoveal choroidal thickness, or axial length was observed. Further well-designed studies should evaluate the long-term effect of isotretinoin on the eye and reach a firmer conclusion.
Topics: Acne Vulgaris; Dry Eye Syndromes; Humans; Isotretinoin; Meibomian Glands; Observational Studies as Topic; Tears
PubMed: 35296199
DOI: 10.1080/15569527.2022.2050747 -
Journal of Glaucoma Jun 2016Comparing the relative effectiveness of interventions across glaucoma trials can be problematic due to differences in definitions of outcomes. We sought to identify a...
PURPOSE
Comparing the relative effectiveness of interventions across glaucoma trials can be problematic due to differences in definitions of outcomes. We sought to identify a key set of clinical outcomes and reach consensus on how best to measure them from the perspective of glaucoma experts.
METHODS
A 2-round electronic Delphi survey was conducted. Round 1 involved 25 items identified from a systematic review. Round 2 was developed based on information gathered in round 1. A 10-point Likert scale was used to quantify importance and consensus of outcomes (7 outcomes) and ways of measuring them (44 measures). Experts were identified through 2 glaucoma societies membership-the UK and Eire Glaucoma Society and the European Glaucoma Society. A Nominal Group Technique (NGT) followed the Delphi process. Results were analyzed using descriptive statistics.
RESULTS
A total of 65 participants completed round 1 out of 320; of whom 56 completed round 2 (86%). Agreement on the importance of outcomes was reached on 48/51 items (94%). Intraocular pressure (IOP), visual field (VF), safety, and anatomic outcomes were classified as highly important. Regarding methods of measurement of IOP, "mean follow-up IOP" using Goldmann applanation tonometry achieved the highest importance, whereas for evaluating VFs "global index mean deviation/defect (MD)" and "rate of VF progression" were the most important. Retinal nerve fiber layer (RNFL) thickness measured by optical coherence tomography (OCT) was identified as highly important. The NGT results reached consensus on "change of IOP (mean of 3 consecutive measurements taken at fixed time of day) from baseline," change of VF-MD values (3 reliable VFs at baseline and follow-up visit) from baseline, and change of RNFL thickness (2 good quality OCT images) from baseline.
CONCLUSIONS
Consensus was reached among glaucoma experts on how best to measure IOP, VF, and anatomic outcomes in glaucoma randomized controlled trials.
Topics: Delphi Technique; Female; Glaucoma; Humans; Intraocular Pressure; Male; Nerve Fibers; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic; Retinal Ganglion Cells; Surveys and Questionnaires; Tomography, Optical Coherence; Tonometry, Ocular; Visual Fields
PubMed: 26091178
DOI: 10.1097/IJG.0000000000000301