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Background/Aim To provide a comprehensive multimodal retinal imaging characterisation of patients with North Carolina macular dystrophy (NCMD). Methods Clinical evaluation and retinal imaging in six families. Results Twenty-one subjects showed phenotypic characteristics of NCMD. Small drusen-like deposits were found in all affected individuals, either tightly grouped in the macula, or surrounding atrophic or fibrotic macular alterations. These small subretinal lesions showed an increased fundus autofluorescence and were associated with only mild irregularities on optical coherence tomography imaging. Similar drusen-like deposits were regularly seen in the peripheral fundus, predominantly temporally and often with a radial distribution. Two patients showed a bilateral chorioretinal atrophy and two had a macular neovascularisation (MNV). Findings from follow-up examinations were available from 11 patients. The retinal phenotype remained overall stable, except for two patients: one patient with atrophy showed a distinct growth of the atrophic lesions on longitudinal AF imaging over a review period of 14 years. One patient with MNV showed a unilateral decline of best-corrected visual acuity. Genetic testing identified the single nucleotide variant chr6:100040987G>C upstream of the PRDM13 gene in all family members with NCMD phenotype. Conclusion Patients with NCMD show a characteristic retinal phenotype and distribution of drusen that differ from drusen in patients with age-related macular degeneration. Although the prognosis of this developmental condition is overall better than for other macular diseases with drusen, patients may be at risk of developing MNV or enlargement of pre-existing atrophy. [ABSTRACT FROM AUTHOR]

Background Loss of photoreceptors cause degeneration in areas of the retina beyond the photoreceptors. The pattern of changes has implications for disease monitoring and measurement of functional changes. The aim of the study was to study the changes in inner retinal structure associated with photoreceptor disease, and the impact of these on microperimetry threshold. Methods This retrospective cohort study was conducted on optical coherence tomography (OCT) images and microperimetry tests collected between 2013 and 2019. 22 eyes with RPGR retinitis pigmentosa completed both OCT imaging and microperimetry assessment. 18 control eyes underwent OCT imaging. Photoreceptor layer and inner retinal thickness calculated for different eccentric areas were obtained. The relationship between the photoreceptor layer and inner retinal thickness, and microperimetry threshold was explored. Results Central 1° photoreceptor layer and inner retinal thickness were 96±34 and 139±75 μm in RPGR patients, and 139±15 and 62±14 μm in controls. Photoreceptor layer thickness differed between patient and control groups across increasing visual field areas (p<0.01, Kruskal-Wallis 1-way ANOVA), whereas the inner retinal thickness significantly differed between groups for the central 1° and 3° only. Microperimetry thresholds were explained by a combination of photoreceptor thickness (coefficient 0.15, 95% CI 0.13 to 0.18) and inner retinal thickness (coefficient 0.05, 95% CI 0.03 to 0.06). Conclusion OCT shows evidence of remodelling in the inner retinal layers secondary to photoreceptor disease. This appears to have an impact on microperimetry threshold measurements. [ABSTRACT FROM AUTHOR]

Background To assess retinal layer thickness in choroideremia (CHM) and to reveal its correlation with optical coherence tomography (OCT) angiography (OCTA) findings. Methods The study was designed as an observational, cross-sectional clinical series of patients with CHM, which included 14 CHM eyes and 14 age-matched controls. Multimodal imaging included OCT and OCTA. The vessel density (VD) of superficial capillary (SCP), deep capillary (DCP) and choriocapillaris (CC) plexuses was analysed by OCTA. The apparently preserved retinal islet and atrophic regions were investigated separately. Main outcome measures were as follows: best-corrected visual acuity (BCVA), total retinal layers, ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), ellipsoid zone-retinal pigment epithelium (EZ-RPE) layer, choroidal thickness and VDs of SCP, DCP and of CC. Results Mean BCVA was 0.0±0.0 LogMAR in both groups. GCL, ONL, EZ-RPE and choroid were significantly thinned in CHM, particularly in the atrophic region. OPL was unaffected in the apparently preserved islet, whereas INL and IPL were similarly thinned in the atrophic and apparently preserved retina. DCP appeared severely affected in both regions, while CC was only altered in the atrophic retina. Significant correlations were found between OCT and OCTA parameters. Conclusions Our study showed severe alterations in both outer and inner retinal layers of patients with CHM. The extended retinal involvement might be the consequence of neuronal and vascular trophic factor reduction produced by the primarily altered RPE and/or secondary Müller glial cell reaction. [ABSTRACT FROM AUTHOR]

Background With the increase in clinical trials testing therapy for retinal disease, there is a need to ensure that outcome measures are both accurate and standardised. The US Food and Drug Administration favours the use of visual acuity measured using ETDRS logMAR charts. The loss of visual field can interfere with visual tracking across the charts, leading to increased variability of measurements. Electronic visual acuity (EVA) presents the optotype on the centre of a screen, thereby removing the tracking element of the task, and may provide a more precise measurement. Methods Visual acuity was measured twice using ETDRS charts, EVA automated single letter (E-ETDRS) and EVA single line (EVA-SL) presentation (EMMES). Patients underwent microperimetry (MAIA; Centervue) to determine visual field. We tested 65 patients with rod-cone dystrophies and 41 healthy volunteers. results Both participant groups read 2-3 letters more on average on the electronic charts compared with ETDRS. Limits of agreement using a modified Bland-Altman analysis account for replicates were wider in eyes with foveal defects (-9 to 18) compared with eyes without foveal defects (-11 to 15). Electronic charts in the presence of foveal defects reduced the range (-11 to 13). Conclusion EVA may provide more accurate measures of visual acuity than traditional ETDRS charts in patients when the visual field loss encroached on the central vision. Electronic presentation with a single line of letters was the favoured style reported by patients and should be considered in future interventional clinical trials. [ABSTRACT FROM AUTHOR]

Background Macular Integrity Assessment (MAIA) microperimetry is increasingly used in clinical and research settings to assess point retinal sensitivity and fixation stability. Testing occurs under mesopic conditions, commonly after a period of dark adaptation. Our aim was to identify the minimum length of adaptation required to optimise microperimetry performance. Methods MAIA microperimetry using the 10-2 grid was performed on 40 right eyes of 40 healthy participants aged 18-73 with no ocular pathology and vision of at least 0.1 logMAR after ambient light exposure, with 0, 5, 10, 15, 20 and 30 min of adaptation in mesopic settings. Ten right eyes of 10 participants with choroideremia were also tested following 0 and 20 min of adaptation. We further tested 10 right eyes of 10 healthy participants after bright light exposure, with 0, 10 and 20 min of adaptation. We compared changes in threshold sensitivity and fixation stability across time points. Results Microperimetry performance did not improve with increasing adaptation time in healthy participants or patients with choroideremia after ambient light exposure. After bright light exposure, we found microperimetry thresholds improved after 10 min of adaptation, but did not improve further at 20 min. Conclusion Mesopic adaptation is not required before MAIA microperimetry after exposure to ambient light. Ten minutes of adaptation is sufficient after exposure to a bright light stimulus, such as ophthalmoscopy or retinal imaging. The brief time of dark adaptation required corresponds to cone adaptation curves and provides further evidence for cone-mediated central retinal function under mesopic conditions. [ABSTRACT FROM AUTHOR]

Background/Aims To better understand the pattern of degeneration progression in cases with choroideremia. Methods A cohort of genotypically confirmed choroideremia cases who underwent optical coherence tomography (OCT) and fundus autofluorescence (FAF) imaging was studied. Using HEYEX review software, the foveal centre was marked on FAF images under guidance of corresponding OCT images, followed by application of an ETDRS grid. The boundaries of preserved autofluorescence (AF) were manually segmented in each individual ETDRS subfield. The regional distribution of preserved AF was assessed by comparing its area among the various subfields. results A total of 168 eyes from 84 choroideremia cases were enrolled. There was a statistically significant difference in the amount of preserved AF area between inner subfields as determined by one-way analysis of variance (F (3,668)=9.997, p<0.001) and also between outer subfields (F (3,668)=8.348, p<0.001). A Tukey posthoc test revealed that the preserved AF area in the nasal subfields in both the inner and outer subfields was significantly smaller compared with analogue subfields. Conclusion The asymmetric spatial distribution of preserved AF in choroideremia (corresponding to the stellate shaped nature of these regions) suggests that the progression of degeneration has directional preference. [ABSTRACT FROM AUTHOR]

Retinitis pigmentosa (RP) relates to a heterogeneous group of rod-cone dystrophies of varying genetic aetiology. There is currently great interest in gene replacement therapy. Phenotyping is of particular importance because some RP genes are expressed ubiquitously and it is critically important to understand which retinal layer is primarily affected. RP2 is increasingly diagnosed in patients suffering from X-linked RP, which causes outer retinal degeneration. We present a case of a previously unreported null mutation in RP2 associated with severe RP. Loss of the retinal pigment epithelium (RPE) was noted in the central macula but not around the disc or peripherally. There was therefore no evidence of independent degeneration of the RPE. Hence despite expression in all retinal cells, RP2 deficiency does not appear to be pathogenic to the RPE. This observation may be helpful in considering the promoter and route of delivery of adenoassociated viral gene therapy vectors encoding RP2. [ABSTRACT FROM AUTHOR]

Purpose To validate three models for predicting proliferative vitreoretinopathy (PVR) based on the analysis of genotypic data and relevant clinical characteristics. Methods The validation series consisted of data from 546 patients operated on from primary rhegmatogenous retinal detachment (RRD) coming from centres in the Netherlands, Portugal, Spain and the UK. Temporal and geographical validation was performed. The discrimination capability of each model was analysed and compared with the original series, using a receiver operating curve. Then, clinical variables were combined in order to improve the predictive capability. A risk reclassification analysis was performed with and without each one of the variables. Reclassification of patients was compared and models were readjusted in the original series. Readjusted models were further validated. Results One of the models showed good predictability in the temporal sample as well as in the original series (area under the curve (AUC) original=0.7352; AUC temporal=0.6457, 95% CI 50.17 to 78.97). When clinical variables were included, only pre-existent PVR improves the predictability of this model in the validation series (temporal and geographical samples) (AUC original=0.7940 vs AUC temporal=0.7744 and AUC geographical=0.7152). The other models showed acceptable AUC values when clinical variables were included although they were less accurate than in the original series. Conclusions Genetic profiling of patients with RRD can improve the predictability of PVR in addition to the wellknown clinical biomarkers. This validated formula could be a new tool in our current clinical practice in order to identify those patients at high risk of developing PVR. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Doctor on a mountaineering expedition," by C. H. D. A'Court et al in the May 13, 1995;310 issue.

A quiz concerning a 22-year-old Pakistani man who was presented with reduced vision of the left eye is presented.

Presents a letter to the editor in response to the article "Recent developments in gene transfer: risks and ethics," by J. Kimmelman, in the January 8, 2005 issue.