Fundus Autofluorescence Imaging Research Articles

Genotype-phenotype severity correlation in a multicentric portuguese cohort of ABCA4-associated retinopathy

PurposeTo investigate genotype-phenotype correlations in ABCA4-associated retinopathy and further validate a recently proposed genotype-phenotype correlation model. DesignMulticentric, cross-sectional cohort study. MethodsConsecutive patients with genetically confirmed ABCA4-associated retinopathy from three Portuguese centres were included. Patients were categorized into distinct phenotype groups according to the degree of hypoautofluorescence and retinal background appearance in ultra-widefield fundus autofluorescence (UW-FAF) imaging. Genotype classification was performed using two criteria: one according to the presence of the p.Gly1961Glu variant, a hypomorphic variant, at least one moderate variant, or two biallelic severe/PVS1 variants (genotype classification A, which corresponds to the newly described criteria); and another one based on the number of null variants identified (genotype classification B). Associations between clinical data and phenotype and genotype groups were analysed. ResultsA total of 50 patients were included. Significant correlations between age of onset, best-corrected visual acuity (BCVA), and both phenotype and genotype groups were found, with patients in more severe phenotype and genotype categories exhibiting earlier disease onset and poorer visual function (p < 0.001; p < 0.001; p < 0.001; p < 0.001, p < 0.001; and p = 0.004, respectively). Genotype classification A better predicted phenotype severity on UW-AF imaging, demonstrating milder genotypes in patients with less severe phenotypes and more severe genotypes in those with advanced disease (p < 0.001). A genotype-phenotype correlation matrix was constructed based on the classification of the two disease-causing variants and their corresponding phenotypic staging. ConclusionOur findings support the utility of the newly described genotype classification in evaluating ABCA4-associated retinopathy phenotype severity, with possible implications in future understanding of the disease genetics and assessment of individual prognosis for patients.

Pegcetacoplan Treatment and Consensus Features of Geographic Atrophy Over 24 Months

Despite widespread availability and consensus on its advantages for detailed imaging of geographic atrophy (GA), spectral-domain optical coherence tomography (SD-OCT) might benefit from automated quantitative OCT analyses in GA diagnosis, monitoring, and reporting of its landmark clinical trials. To analyze the association between pegcetacoplan and consensus GA SD-OCT end points. This was a post hoc analysis of 11 614 SD-OCT volumes from 936 of the 1258 participants in 2 parallel phase 3 studies, the Study to Compare the Efficacy and Safety of Intravitreal APL-2 Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (OAKS) and Study to Compare the Efficacy and Safety of Intravitreal APL-2 Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (DERBY). OAKS and DERBY were 24-month, multicenter, randomized, double-masked, sham-controlled studies conducted from August 2018 to July 2020 among adults with GA with total area 2.5 to 17.5 mm2 on fundus autofluorescence imaging (if multifocal, at least 1 lesion ≥1.25 mm2). This analysis was conducted from September to December 2023. Study participants received pegcetacoplan, 15 mg per 0.1-mL intravitreal injection, monthly or every other month, or sham injection monthly or every other month. The primary end point was the least squares mean change from baseline in area of retinal pigment epithelium and outer retinal atrophy in each of the 3 treatment arms (pegcetacoplan monthly, pegcetacoplan every other month, and pooled sham [sham monthly and sham every other month]) at 24 months. Feature-specific area analysis was conducted by Early Treatment Diabetic Retinopathy Study (ETDRS) regions of interest (ie, foveal, parafoveal, and perifoveal). Among 936 participants, the mean (SD) age was 78.5 (7.22) years, and 570 participants (60.9%) were female. Pegcetacoplan, but not sham treatment, was associated with reduced growth rates of SD-OCT biomarkers for GA for up to 24 months. Reductions vs sham in least squares mean (SE) change from baseline of retinal pigment epithelium and outer retinal atrophy area were detectable at every time point from 3 through 24 months (least squares mean difference vs pooled sham at month 24, pegcetacoplan monthly: -0.86 mm2; 95% CI, -1.15 to -0.57; P < .001; pegcetacoplan every other month: -0.69 mm2; 95% CI, -0.98 to -0.39; P < .001). This association was more pronounced with more frequent dosing (pegcetacoplan monthly vs pegcetacoplan every other month at month 24: -0.17 mm2; 95% CI, -0.43 to 0.08; P = .17). Stronger associations were observed in the parafoveal and perifoveal regions for both pegcetacoplan monthly and pegcetacoplan every other month. These findings offer additional insight into the potential effects of pegcetacoplan on the development of GA, including potential effects on the retinal pigment epithelium and photoreceptors. ClinicalTrials.gov Identifiers: NCT03525600 and NCT03525613.

When Two Eyes Don't Suffice-Learning Difficult Hyperfluorescence Segmentations in Retinal Fundus Autofluorescence Images via Ensemble Learning.

Hyperfluorescence (HF) and reduced autofluorescence (RA) are important biomarkers in fundus autofluorescence images (FAF) for the assessment of health of the retinal pigment epithelium (RPE), an important indicator of disease progression in geographic atrophy (GA) or central serous chorioretinopathy (CSCR). Autofluorescence images have been annotated by human raters, but distinguishing biomarkers (whether signals are increased or decreased) from the normal background proves challenging, with borders being particularly open to interpretation. Consequently, significant variations emerge among different graders, and even within the same grader during repeated annotations. Tests on in-house FAF data show that even highly skilled medical experts, despite previously discussing and settling on precise annotation guidelines, reach a pair-wise agreement measured in a Dice score of no more than 63-80% for HF segmentations and only 14-52% for RA. The data further show that the agreement of our primary annotation expert with herself is a 72% Dice score for HF and 51% for RA. Given these numbers, the task of automated HF and RA segmentation cannot simply be refined to the improvement in a segmentation score. Instead, we propose the use of a segmentation ensemble. Learning from images with a single annotation, the ensemble reaches expert-like performance with an agreement of a 64-81% Dice score for HF and 21-41% for RA with all our experts. In addition, utilizing the mean predictions of the ensemble networks and their variance, we devise ternary segmentations where FAF image areas are labeled either as confident background, confident HF, or potential HF, ensuring that predictions are reliable where they are confident (97% Precision), while detecting all instances of HF (99% Recall) annotated by all experts.

Comprehensive analysis of two hotspot codons in the TUBB4B gene and associated phenotypes

Our purpose was to elucidate the genotype and ophthalmological and audiological phenotype in TUBB4B-associated inherited retinal dystrophy (IRD) and sensorineural hearing loss (SNHL), and to model the effects of all possible amino acid substitutions at the hotspot codons Arg390 and Arg391. Six patients from five families with heterozygous missense variants in TUBB4B were included in this observational study. Ophthalmological testing included best-corrected visual acuity, fundus examination, optical coherence tomography, fundus autofluorescence imaging, and full-field electroretinography (ERG). Audiological examination included pure-tone and speech audiometry in adult patients and auditory brainstem response testing in a child. Genetic testing was performed by disease gene panel analysis based on genome sequencing. The molecular consequences of the substitutions of residues 390 and 391 on TUBB4B and its interaction with α-tubulin were predicted in silico on its three-dimensional structure obtained by homology modelling. Two independent patients had amino acid exchanges at position 391 (p.(Arg391His) or p.(Arg391Cys)) of the TUBB4B protein. Both had a distinct IRD phenotype with peripheral round yellowish lesions with pigmented spots and mild or moderate SNHL, respectively. Yet the phenotype was milder with a sectorial pattern of bone spicules in one patient, likely due to a genetically confirmed mosaicism for p.(Arg391His). Three patients were heterozygous for an amino acid exchange at position 390 (p.(Arg390Gln) or p.(Arg390Trp)) and presented with another distinct retinal phenotype with well demarcated pericentral retinitis pigmentosa. All showed SNHL ranging from mild to severe. One additional patient showed a variant distinct from codon 390 or 391 (p.(Tyr310His)), and presented with congenital profound hearing loss and reduced responses in ERG. Variants at codon positions 390 and 391 were predicted to decrease the structural stability of TUBB4B and its complex with α-tubulin, as well as the complex affinity. In conclusion, the twofold larger reduction in heterodimer affinity exhibited by Arg391 substitutions suggested an association with the more severe retinal phenotype, compared to the substitution at Arg390.

Genotypic and phenotypic characterization of a cohort of patients affected by rod CNG channel-associated retinitis pigmentosa.

Retinitis pigmentosa (RP), a heterogeneous inherited retinal disorder causing gradual vision loss, affects over 1 million people worldwide. Pathogenic variants in CNGA1 and CNGB1 genes, respectively accounting for 1% and 4% of cases, impact the cyclic nucleotide-gated channel in rod photoreceptor cells. The aim of this study is to describe and compare genotypic and clinical characteristics of a cohort of patients with CNGA1- or CNGB1-related RP and to explore potential genotype-phenotype correlations. The following data from patients with CNGA1- or CNGB1-related RP, followed in five Italian inherited retinal degenerations services, were retrospectively collected: genetic variants in CNGA1 and CNGB1, best-corrected visual acuity (BCVA), ellipsoid zone (EZ) width, fundus photographs and short-wavelength fundus autofluorescence (SW-AF) images. Comparisons and correlation analyses were performed by first dividing the cohort in two groups according to the gene responsible for the disease (CNGA1 and CNGB1 groups). In parallel, the whole cohort of RP patients was divided into two other groups, according to the expected impact of the variants at protein level (Low and High group). In total, 29 patients were recruited, 11 with CNGA1- and 18 with CNGB1-related RP. In both CNGA1 and CNGB1, 5 novel variants in CNGA1 and 5 in CNGB1 were found. BCVA was comparable between CNGA1 and CNGB1 groups, as well as between Low and High groups. CNGA1 group had a larger mean EZ width compared to CNGB1 group, albeit not statistically significant, while EZ width did not differ between Low and High groups A statistically significant correlation between EZ width and BCVA as well as between EZ width and age were observed in the whole cohort of RP patients. Fundus photographs of all patients in the cohort showed classic RP pattern, and in SW-AF images an hyperautofluorescent ring was observed in 14/21 patients. Rod CNG channel-associated RP was demonstrated to be a slowly progressive disease in both CNGA1- and CNGB1-related forms, making it an ideal candidate for gene augmentation therapies.

Clinical predictive factors and imaging biomarkers of treatment response to half dose PDT in patients with chronic central serous chorioretinopathy

PurposeTo determine the clinical and imaging biomarkers of the response to half-dose photodynamic therapy (HD-PDT) in patients with central serous chorioretinopathy (CSC) MethodsClinical records and baseline ophthalmic images of 67 chronic CSC patients who underwent HD-PDT were assessed. In addition to demographic data, optical coherence tomography (OCT), fluorescein angiography (FA) and fundus autofluorescence (FAF) images were analyzed for specific biomarkers. The patients were categorized to early responder and late responder based on the time needed for complete resolution of subretinal fluid after PDT (less than 1 month vs. more than 1 month). The baseline clinical and imaging biomarkers were compared between the two groups. ResultsSeventy-three eyes of 67 patients were included in the study. The mean response time to PDT was 1.63 ± 1.48 months with 82.2 % (60/73) of patients categorized as early responder. The mean response time to PDT in delayed-response group was 4.15±1.51 months. In multivariate analysis, delayed response to PDT was associated with lacking history of systemic corticosteroid consumption, lacking history of pretreatment with eplerenone or acetazolamide before PDT and presence of hyperreflective foci in baseline OCT images (all p values < 0.05). There was no association between final visual outcome and late response to PDT. ConclusionThe presence of inflammatory biomarkers such as hyperreflective foci in baseline OCT images might be indicative of resistance to PDT. Moreover, the effect of pretreatment with mineralocorticoid antagonist on the response to PDT in chronic CSC should be explored in future prospective studies.

Correlation Between Blue Fundus Autofluorescence and SD-OCT Measurements of Geographic Atrophy in Dry Age-Related Macular Degeneration

To compare fundus autofluorescence (FAF) and spectral domain-optical coherence tomography (OCT) measurements of geographic atrophy (GA) area and to analyze lesion area changes measured by SD-OCT in GATHER1. An assessment reliability analysis using prospective, randomized, double-masked phase 2/3 clinical trial data. GATHER1 examined the efficacy and safety of avacincaptad pegol (ACP) for GA treatment. A post hoc analysis was performed to identify correlations between FAF- and OCT-based measurements of GA. GA area was measured on blue-light FAF images using semiautomatic segmentation software with support from OCT and near infrared imaging. Machine-learning enhanced, multilayer segmentation of OCT scans were reviewed by human readers, and segmentation errors were corrected as needed. GA area was defined as total RPE loss on cross-sectional B scans. Time points included Months 0, 6, 12, and 18. Additionally, OCT-based GA-area changes between ACP and sham were analyzed. There was a strong correlation (r=0.93) between FAF and OCT GA area measurements that persisted through 18 months. Mean (SD) differences between OCT and FAF GA measurements were negligeable: 0.11 mm2 (1.42) at Month 0, 0.03 mm2 (1.62) at Month 6, -0.17 mm2 (1.81) at Month 12, and -0.07 mm2 (1.78) at Month 18. OCT assessments of GA growth revealed a 30% and 27% reduction at Months 12 and 18, respectively, between ACP and sham, replicating FAF measurements from GATHER1. The strong correlation between blue FAF and OCT measurements of GA area supports OCT as a reliable method to measure GA lesion area in clinical trials.

Systematic study of ophthalmological findings in 10 patients with PEX1-mediated Zellweger spectrum disorder

ABSTRACT Purpose This cross-sectional study describes the ophthalmological and general phenotype of 10 patients from six different families with a comparatively mild form of Zellweger spectrum disorder (ZSD), a rare peroxisomal disorder. Methods Ophthalmological assessment included best-corrected visual acuity (BCVA), perimetry, microperimetry, ophthalmoscopy, fundus photography, spectral-domain optical coherence tomography (SD-OCT), and fundus autofluorescence (FAF) imaging. Medical records were reviewed for medical history and systemic manifestations of ZSD. Results Nine patients were homozygous for c.2528 G > A (p.Gly843Asp) variants in PEX1 and one patient was compound heterozygous for c.2528 G>A (p.Gly843Asp) and c.2097_2098insT (p.Ile700TyrfsTer42) in PEX1. Median age was 22.6 years (interquartile range (IQR): 15.9 – 29.9 years) at the most recent examination, with a median symptom duration of 22.1 years. Symptom onset was variable with presentations of hearing loss (n = 7) or nyctalopia/reduced visual acuity (n = 3) at a median age of 6 months (IQR: 1.9–8.3 months). BCVA (median of 0.8 logMAR; IQR: 0.6–0.9 logMAR) remained stable over 10.8 years and all patients were hyperopic. Fundus examination revealed a variable retinitis pigmentosa (RP)-like phenotype with rounded hyperpigmentations as most prominent feature in six out of nine patients. Electroretinography, visual field measurements, and microperimetry further established the RP-like phenotype. Multimodal imaging revealed significant intraretinal fluid cavities on SD-OCT and a remarkable pattern of hyperautofluorescent abnormalities on FAF in all patients. Conclusion This study highlights the ophthalmological phenotype resembling RP with moderate to severe visual impairment in patients with mild ZSD. These findings can aid ophthalmologists in diagnosing, counselling, and managing patients with mild ZSD.

Clinical Characteristics and Progression of Pachychoroid and Conventional Geographic Atrophy

PurposeTo elucidate the clinical characteristics and progression rates of pachychoroid and conventional geographic atrophy (GA). DesignRetrospective, multicenter, observational study. ParticipantsA total of 173 eyes from 173 patients (38 eyes with pachychoroid GA and 135 with conventional GA) from six university hospitals in Japan were included. All patients were Japanese, aged ≥ 50 years and with fundus autofluorescence (FAF) images having analyzable image quality. A total of 101 eyes (22 with pachychoroid GA and 79 with conventional GA) were included in the follow-up group. MethodsThe studied eyes were classified as having pachychoroid or conventional GA; the former was diagnosed if the eye had features of pachychoroid and no drusen. The GA area was semi-automatically measured on FAF images, and the GA progression rate was calculated for the follow-up group. Multivariable linear regression analysis was used to determine whether the rate of GA progression was associated with GA subtype. Main Outcome MeasuresClinical characteristics and progression rates of pachychoroid and conventional GA. ResultsThe pachychoroid GA group was significantly younger (70.3 vs. 78.7 years, P < 0.001), more male-dominant (89.5 vs. 55.6 %, P < 0.001), and had better best-corrected visual acuity (0.15 vs. 0.40 in logarithm of the minimum angle of resolution, P = 0.002), thicker choroid (312.4 vs. 161.6 μm, P < 0.001), higher rate of unifocal GA type (94.7 vs. 49.6%, P < 0.001), and smaller GA area (0.59 vs. 3.76 mm2, P < 0.001) than the conventional GA group. In the follow-up group, the mean GA progression rate (square-root transformation) was significantly lower in the pachychoroid GA group than in the conventional GA group (0.11 vs 0.27 mm/year, P < 0.001). ConclusionsDemographic and ocular characteristics differed between GA subtypes. The progression rate of pachychoroid GA, adjusted for age and baseline GA area, was significantly lower than that of conventional GA. Japanese patients with conventional GA showed characteristics and progression rates similar to those in Caucasian populations. Some characteristics of GA in Japanese population differ from those in Caucasian populations, which may be due to the inclusion of pachychoroid GA.

Electrodiagnostic Biomarkers in Paraneoplastic Retinopathy.

Paraneoplastic retinopathy (PNR) is a rapid-onset photoreceptor and post-photoreceptor dysfunction triggered by a cross-reaction between antigens expressed by the underlying tumour and retinal proteins. The present study aims to determine the electrodiagnostic biomarkers that support the diagnosis of PNR and evaluate the effect of treatment. A retrospective observational case-controlled study including 25 patients with suspected PNR, of which 11 patients were diagnosed with PNR. The presence of PNR was confirmed based on clinical examination, supported by colour fundus photography, fundus autofluorescence imaging, optical coherence tomography, fluorescein angiography, retinal vessel oximetry, colour test, full-field electroretinogram (ffERG), on-/off ERG, S-cone ERG, and multifocal ERG (mfERG). The relationships between the clinical symptomatology and the effect of therapy were evaluated. All PNR patients (Nr: 11) presented with subjective symptoms of newly reported central vision or visual field deterioration. Posterior segment findings showed a severe patchy-like retinal atrophy, attenuation of the retinal vessels, and a waxy optic disc. Optical coherence tomography revealed a discontinued ISe line, and multiple hyperreflective foci. Retinal vessel oxygen saturation was increased. Multifocal ERG revealed reduced central and paracentral responses and ffERG severely attenuated scotopic-, photopic-, on-/off- and S-cone responses. The colour vision test revealed a tritan-tetartan-weakness. Two of the PNR patients underwent rituximab therapy with no further progression and even recovery of electrodiagnostic responses.In 1 nPNR (non-paraneoplastic retinopathy) patient (total Nr: 14) pseudoxanthoma elasticum-related retinopathy was the reason for impaired vision. In 3 of 13 patients with bronchopulmonary cancer a MEK- and FGFR-inhibitor- drug toxicity was the reason for the visual deterioration. Careful investigation for signs of central and/or peripheral visual field deterioration must be performed in the presence of history of a co-existing malignancy. The possibility of PNR should be taken into account. The electrodiagnostic biomarkers, suggested in this study, may help to promptly recognise PNR and also to evaluate the effect of implemented therapy.

Comparison of Blue-Light Autofluorescence and Ultrawidefield Green-Light Autofluorescence for Assessing Geographic Atrophy

The goal of this study was to evaluate and compare the inter-modality and inter-reader agreement of manual and semiautomated GA (Geographic Atrophy) area measurements in eyes with GA due to age-related macular degeneration (AMD) using conventional blue and ultrawidefield (UWF) green light fundus autofluorescence (FAF) systems. FAF images of eyes with GA were obtained during a single visit using both the Spectralis HRA+OCT2 device and the Optos California device. Images were exported for masked analysis by two independent masked graders. The area of the GA lesion(s) was segmented and quantified (mm2) with a fully manual approach where the lesions were outlined using Optos Advance and Heidelberg Eye Explorer (HEYEX) software. In addition, for the Heidelberg blue FAF images, GA lesions were also measured using the instrument's semi-automated software (Region Finder 2.6.4). For comparison between modalities/grading method, the mean values of the two graders were used. Intraclass correlation coefficients (ICC) were computed to judge the agreement between graders. 72 eyes of 50 patients were included in this study. There was nearly perfect agreement between graders for the measurement of GA area for all three modalities (Intraclass Correlation coefficient = 0.996 for manual Optos Advance, 0.996 for manual Heidelberg HEYEX, 0.995 for Heidelberg Region Finder). The measurement of GA area was strongly correlated between modalities, with Spearman correlation coefficients of 0.985 (p < 0.001) between manual Heidelberg and manual Optos, 0.991 (p < 0.001) for Region Finder versus manual Heidelberg, and 0.985 (p < 0.001) for Region Finder versus manual Optos. The absolute mean area differences between the Heidelberg manual vs Region Finder, manual Optos vs Region Finder, and manual Optos vs manual Heidelberg were 1.61 mm2 (p<0.001), 0.90 mm2 (p<0.001), and 0.71 mm2 (p<0.001), respectively. We observed excellent inter-reader agreement for measurement of GA using either 30-degree blue FAF or UWF green FAF, establishing the reliability of UWF imaging for macular GA assessment. While the absolute measurements between devices were strongly correlated, they differed significantly, highlighting the importance of using the same device for a given patient for the duration of a study.

Impact of lens autofluorescence and opacification on retinal imaging

BackgroundRetinal imaging, including fundus autofluorescence (FAF), strongly depends on the clearness of the optical media. Lens status is crucial since the ageing lens has both light-blocking and autofluorescence (AF) properties...

Circular Perivascular Autofluorescence Pattern in Patients With Autoimmune Retinopathy.

Purpose: To report the characteristics and prevalence of a previously undescribed circular perivascular fundus autofluorescence (FAF) pattern in paraneoplastic and nonparaneoplastic autoimmune retinopathy. Methods: This retrospective case series used clinical and imaging data extracted from charts of patients with autoimmune retinopathy in whom FAF imaging was performed from the initial presentation to the last visit. Results: Six of 25 patients with autoimmune retinopathy and FAF imaging developed circular perivascular FAF changes. Three patients had paraneoplastic autoimmune retinopathy, and 3 had nonparaneoplastic autoimmune retinopathy. The lesions appeared a mean of 25 months after symptom onset; however, the timing varied from months to years and did not correlate with the overall disease course. The lesions were initially typically hyperautofluorescent and varied in progression, distribution, and quality. Optical coherence tomography showed hyperreflective subretinal deposits in the corresponding areas in most patients. Conclusions: To our knowledge, these are the first reported cases with this circular perivascular FAF pattern in nonparaneoplastic autoimmune retinopathy. This finding could also be a useful diagnostic imaging marker in some patients with autoimmune retinopathy.

Longitudinal Adaptive Optics Scanning Laser Ophthalmoscopy Reveals Regional Variation in Cone and Rod Photoreceptor Loss in Stargardt Disease.

To investigate the temporal sequence of changes in the photoreceptor cell mosaic in patients with Stargardt disease type 1 (STGD1), using adaptive optics scanning laser ophthalmoscopy (AOSLO). Two brothers with genetically confirmed STGD1 underwent comprehensive eye exams, spectral-domain optical coherence tomography (SD-OCT), fundus auto fluorescence (FAF) and AOSLO imaging 3 times over the course of 28 months. Confocal images of the cones and rods were obtained from the central fovea to 10 degrees inferiorly. Photoreceptors were counted in sampling windows at 100 µm intervals of 200 µm × 200 µm for cones and 50 µm × 50 µm for rods, using custom cell marking software with manual correction. Photoreceptor density and spacing were measured and compared across imaging sessions using one-way ANOVA. AOSLO revealed the younger brother had a 30% decline in foveal cone density after 8 months, followed by complete loss of foveal cones at 28 months; the older brother had no detectable foveal cones at baseline. In the peripheral macula, cone and rod spacings were greater than normal in both patients. The ratio of the cone spacing to rod spacing was greater than normal across all eccentricities, with a greater divergence closer to the foveal center. Cone cell loss may be an early pathogenetic step in Stargardt disease. AOSLO provides the capability to track individual photoreceptor changes longitudinally in Stargardt disease. The pathogenetic mechanism of Stargardt disease remains poorly understood. We used high resolution AOSLO to track the progression of the disease and found cone cell loss may be an early pathogenetic step in Stargardt disease.

Subthreshold laser treatment for non-center involved diabetic macular edema via non-damaging retinal laser therapy (NRT).

To evaluate the efficacy of subthreshold laser treatment via non-damaging retinal laser therapy (NRT) in patients with non-center involved diabetic macular edema (non-CI DME). In this prospective controlled study, NRT with 577nm wavelength was performed to the edematous inner subfields as needed at 3 monthly intervals, while the control group received no treatment. If CI-DME developed in either group, intravitreal anti-VEGF was performed and the eye was excluded from subsequent analysis. A total of 75 eyes (36 study eyes, 39 controls) were evaluated. The change in superior, nasal and temporal inner subfield thicknesses over time and between groups was found significant (P = 0.004, P < 0.001, P = 0.04 respectively). Best corrected visual acuity (BCVA) change was not significant over time and between groups (P = 0.69). Rates of CI-DME development requiring intravitreal anti-VEGF treatment were not different during the first and second years (P = 0.171, 0.908). No laser scar was detected in any eye in fundus autofluorescence imaging. NRT performed as needed at 3 monthly intervals is effective after 21months of follow up in the treatment of non-CI DME and it was safe. With this method, it may be foreseen that BCVA will be better preserved in the long term by avoiding the possible side effects of conventional laser.

The impact of short-term postoperative face-up position on unintentional retinal displacement after pars plana vitrectomy for rhegmatogenous retinal detachment.

To assess the effectiveness and safety of a rigorous short-term supine position in preventing inadvertent retinal displacement after pars plana vitrectomy (PPV) with gas tamponade for rhegmatogenous retinal detachment (RRD). We conducted a retrospective observational analysis of a case series at two ophthalmological surgical centers. We included eyes diagnosed with macula-off RRD that maintained a strict face-up position for three hours immediately after PPV with intraoperative perfluorocarbon liquid (PFCL) and 20% sulfur hexafluoride (SF6) tamponade. Fundus autofluorescence (FAF) imaging was performed at one month post-operatively to identify unintentional retinal displacement through the detection of retinal vessel prints (RVPs) on FAF imaging using an ultrawide-field (UWF) imaging system. A total of 29 eyes with macula-off RRD were included in the study. The average age of the participants was 59.62 years. RRD involved one quadrant in two eyes, two quadrants in fourteen eyes, three quadrants in seven eyes, and four quadrants in six eyes. UWF-FAF imaging at one month follow-up after complete reattachment of the retina revealed RVPs in seven out of the 29 eyes (24.13%), with a mean displacement of 0.22 mm. In every case the displacement occurred downward. Our results suggest that adhering to a strict face-up position for three hours after PPV with PFCL and gas tamponade for macula-off RRD may lead to a low frequency and severity of inadvertent post-operative retinal displacement.

Shwachman-Diamond syndrome associated with rod-cone dystrophy.

To report a patient with Shwachman-Diamond syndrome and concomitant rod-cone dystrophy who underwent bone marrow transplantation. Retrospective single case report. A female patient with Shwachman-Diamond syndrome was referred to a tertiary hospital to investigate possible pigmentary retinopathy at the age of 16. She described poor night vision and was found to have reduced visual acuity (6/20 right, 6/38 left). Over the ten-year follow-up period, her visual acuity remained relatively stable with no new visual symptoms. Optical coherence tomography revealed progressive, diffuse outer retinal thinning with disruption of the ellipsoid zone, which initially was relatively preserved subfoveally. Fundus autofluorescence images revealed generalised areas of hypoautofluorescence beyond the vascular arcades and a perimacular ring of increased autofluorescence. The flash electroretinogram was in keeping with a severe rod-cone dystrophy. The pattern visual evoked potential was abnormal but detectable indicating macular pathway dysfunction, suggesting encroachment into central macular regions but with some functional preservation. We report a patient with Shwachman-Diamond syndrome with severe early-onset rod-cone dystrophy noted at the age of 16. Slow anatomical progression has been observed over the subsequent ten years, with relative functional macular preservation to support a visual acuity of 6/36 in both eyes.

ATXN7-Related Cone-Rod Dystrophy

Reliable biomarkers with diagnostic and prognostic values are needed for upcoming gene therapy trials for spinocerebellar ataxias. To identify ophthalmological biomarkers in a sample of spinocerebellar ataxia type 7 (SCA7) carriers. This article presents baseline data from a cross-sectional natural history study conducted in Paris, France, reference centers for rare diseases from May 2020 to April 2021. Data were analyzed from September to December 2022. Fifteen adult ATXN7 pathogenic expansion carriers (9 with preataxia and 6 with ataxia) were included, all with a Scale for the Assessment and Rating of Ataxia (SARA) score of 15 of 40 or lower. Patients were recruited at the Paris Brain Institute, and all contacted patients accepted to participate in the study. Three visits (baseline, 6 months, and 12 months) were planned, including neurological examination (SARA and Composite Cerebellar Functional Severity Score), ophthalmological examination (best-corrected visual acuity, microperimetry, full-field electroretinogram, optical coherence tomography, and fundus autofluorescence imaging), and neurofilament light chain (NfL) measurements. Here we report the baseline ophthalmic data from the cohort and determine whether there is a correlation between disease scores and ophthalmic results. Among the 15 included SCA7 carriers (median [range] age, 38 [18-60] years; 8 women and 7 men), 12 displayed cone or cone-rod dystrophy, with the number of CAG repeats correlating with disease severity (ρ, 0.73, 95% CI, 0.34 to 0.90; P < .001). Two patients with cone-rod dystrophy exhibited higher repeat numbers and greater ataxia scores (median [range] SARA score, 9 [7-15]) compared to those with only cone dystrophy (median [range] SARA score, 2 [0-5]). A correlation emerged for outer nuclear layer thickness with SARA score (ρ, -0.88; 95% CI, -0.96 to -0.59; P < .001) and NfL levels (ρ, -0.87; 95% CI, -0.86 to 0.96; P < .001). Moreover, ataxia severity was correlated with visual acuity (ρ: 0.89; 95% CI, 0.68 to 0.96; P < .001) and retinal sensitivity (ρ, -0.88; 95% CI, -0.96 to 0.59; P < .001). In this cross-sectional study, retinal abnormalities were found at preataxic stages of the disease. Most of the carriers presented with cone dystrophy and preserved rod function. The outer nuclear layer thickness correlated with SARA score and plasma NfL levels suggesting nuclear layer thickness to be a biomarker of disease severity. These findings contribute to understanding the dynamics of SCA7-related retinal dystrophy and may help lay the groundwork for future therapeutic intervention monitoring and clinical trials. ClinicalTrials.gov Identifier: NCT04288128.

Automated identification of fleck lesions in Stargardt disease using deep learning enhances lesion detection sensitivity and enables morphometric analysis of flecks

PurposeTo classify fleck lesions and assess artificial intelligence (AI) in identifying flecks in Stargardt disease (STGD).MethodsA retrospective study of 170 eyes from 85 consecutive patients with confirmed STGD. Fundus autofluorescence...

Genetics, Clinical Characteristics, and Natural History of PDE6B-Associated Retinal Dystrophy

To analyze the clinical characteristics, natural history, and genetics of PDE6B-associated retinal dystrophy. Retrospective, observational cohort study. Review of medical records and retinal imaging, including fundus autofluorescence (FAF) imaging and spectral-domain optical coherence tomography (SD-OCT) of patients with molecularly confirmed PDE6B-associated retinal dystrophy in a single tertiary referral center. Genetic results were reviewed, and the detected variants were assessed. Forty patients (80 eyes) were identified and evaluated longitudinally. The mean age (±SD, range) was 42.1 years (± 19.0, 10-86) at baseline, with a mean follow-up time of 5.2 years. Twenty-nine (72.5%) and 27 (67.5%) patients had no or mild visual acuity impairment at baseline and last visit, respectively. Best-corrected visual acuity (BCVA) was 0.56 ± 0.72 LogMAR (range -0.12 to 2.80) at baseline and 0.63 ± 0.73 LogMAR (range 0.0-2.80) at the last visit. BCVA was symmetrical in 87.5% of patients. A hyperautofluorescent ring was observed on FAF in 48 and 46 eyes at baseline and follow-up visit, respectively, with a mean area of 7.11 ± 4.13 mm2 at baseline and mean of 6.13 ± 3.62 mm2 at the follow-up visit. Mean horizontal ellipsoid zone width at baseline was 1946.1 ± 917.2 µm, which decreased to 1763.9 ± 827.9 µm at follow-up. Forty-four eyes had cystoid macular edema at baseline (55%), and 41 eyes (51.3%) at follow-up. There were statistically significant changes during the follow-up period in terms of BCVA and the ellipsoid zone width. Genetic analysis identified 43 variants in the PDE6B gene, including 16 novel variants. This study details the natural history of PDE6B-retinopathy in the largest cohort to date. Most patients had mild to no BCVA loss, with slowly progressive disease, based on FAF and OCT metrics. There is a high degree of disease symmetry and a wide window for intervention.