Rare occult macular dystrophy with a pathogenic variant in the RP1L1 gene in a patient of Swiss descent.

Purpose: We report a first case of bilateral occult macular dystrophy (OMD) with a c.133C>T (p.Arg45Trp) pathogenic variant in the retinitis pigmentosa 1-like 1 (RP1L1) gene in a patient of Caucasian Swiss decent. Observations: A 34-year-old man presented with decreased visual acuity known since childhood. Fundus examination of both eyes revealed no pathology other than mildly increased granularity of the foveal retinal pigment epithelium. The full-field electroretinogram (ffERG) presented with normal findings while the multifocal electroretinogram (mfERG) showed severely reduced amplitudes of the foveal response. Optical coherence tomography (OCT) showed foveal outer retinal atrophy. Fundus autofluorescence (FAF) imaging demonstrated near-normal findings with minimal mottling at the posterior pole. The genetic analysis revealed a heterozygous pathogenic variant (c.133C>T, p.Arg45Trp) in the RP1L1 gene. Conclusion and importance: Our present case suggests that OMD shows a wide range of clinical presentations with a variety of ophthalmological findings, age of disease onset, visual acuity, and genetic diversity.

Full-field sensitivity threshold and the relation to the oxygen metabolic retinal function in retinitis pigmentosa.

PURPOSE: The aim of our study was to evaluate retinal function with white light dark-adapted full-field sensitivity threshold (FST) and find possible correlations with metabolic function measured with retinal oximetry (RO) in patients with retinitis pigmentosa (RP). METHODS: In this prospective observational study (BASEC 2020-00,122), FST and RO measurements were performed on 66 RP eyes (33 subjects, 12♀ 21♂) aged between 18 and 80 years (mean 43.2 years); all eyes were graded for disease severity. Main outcome parameters were white FST thresholds using the Diagnosys Espion system with the ColorDomeTM LED full-field stimulator (Diagnosys LLC, Lowell, MA) as well as the main RO parameters: the mean arterial (A-SO2; %), venular (V-SO2; %) oxygen saturation, their difference (A-V SO2; %), and the corresponding mean diameters of the peripapillary retinal arterioles (D-A; µm) and venules (D-V; µm) recorded with the oxygen saturation tool of the Retinal Vessel Analyser (RVA; IMEDOS Systems UG, Jena, Germany). In addition, semi-automated kinetic perimetry (V4e, III4e, I4e, III3e isopters, Octopus 900®, Haag-Streit AG Bern, Switzerland) was performed and included in the linear mixed-effects models analysis calculated with SPSS®. RESULTS: Neither the oxygen saturation parameters (p > 0.21) nor the D-A and D-V (p > 0.13) showed significant correlations with the FST. However, when compared systematically with the visual field (VF) areas of the different isopters, RO parameters V-SO2 (p = 0.024) and A-V SO2 (p < 0.02) showed significant correlations. Furthermore, both V-SO2 and A-V SO2 showed gradual changes with more pronounced impairment in oxygen metabolic function in advanced stages of RP when analyzed in subgroups of disease severity grades. CONCLUSION: In contrast to standardized VF parameters, white dark-adapted FST appears not to correlate with retinal oxygen metabolic function measured with RO in patients with RP, suggesting that the two examinations may capture unrelated aspects of the retinal pathological process. However, RO showed a significant association with standardized VF testing parameters and may, therefore, offer an alternative outcome measure for interventional trials.

Metabolic Long-Term Monitoring of Transcorneal Electrical Stimulation in Retinitis Pigmentosa.

INTRODUCTION: Transcorneal electrical stimulation (TES) is a new therapeutical approach for retinitis pigmentosa (RP). With progression of RP, degeneration of photoreceptors results in lower oxygen consumption of the retina. Retinal oximetry (RO) is a noninvasive method to analyze oxygen saturation in retinal vessels and has shown promising short-term results as a therapy monitoring tool for TES. The aim of our study was to measure the long-term effects of TES on RO parameters over a period of 3 years (3Y). METHODS: A total of 18 eyes of 9 subjects (5♀ 4♂) suffering from RP were examined at baseline (BL), 6 months, and 3Y of TES (OkuStim®) treatment. TES was performed for 30 min once a week at 200% of the individual phosphene threshold simultaneously on both eyes. The oxygen saturation was examined at BL and following TES therapy with the oxygen saturation tool of the Retinal Vessel Analyser (IMEDOS Systems UG, Jena, Germany). The global oxygen saturation parameters (in %), within 1.0-1.5 optic-disc diameters from the disc margin, in retinal arterioles (A-SO2) and venules (V SO2) were measured and their difference (A-V SO2) was calculated. In addition, we recorded the diameters in the main arterioles (D-A) and venules (D-V). ANOVA-based linear mixed-effects models were employed for statistical analysis using SPSS®. RESULTS: After 3Y of TES treatment both the mean A-SO2 (from 96.35 ± 12.76% to 100.89 ± 5.87%, p = 0.22) and V SO2 (from 62.20 ± 11.55% to 64.55 ± 8.24%, p = 0.77) increased slightly. The A-V SO2, which corresponds to the oxygen consumption of the retina, presented also with a slight increment from 34.15 ± 9.68% at BL to 36.23 ± 7.71% without reaching statistical significance (p = 0.27). TES also did not appear to alter the vascular diameter parameters, D-A and D-V (p > 0.05). CONCLUSION: Our long-term observations indicate that TES therapy in RP might lead to a slight increment in oxygen consumption of the retina. However, a larger cohort and longer duration may be needed to adequately power a follow-up study and to confirm this trend reflecting a possible benefit of TES for RP.

Microvascular and metabolic alterations in retinitis pigmentosa and Stargardt disease.

PURPOSE: The aim of our study was to evaluate retinal microvascular changes recorded with optical coherence tomography angiography (OCTA) and the metabolic function measured with retinal oximetry (RO) in patients with retinitis pigmentosa (RP) and Stargardt disease (STGD). METHODS: In this prospective, noninterventional study, OCTA and RO were performed on 107 eyes (56 subjects): 53 eyes diagnosed with RP without the presence of macular oedema (no-ME-RP), 26 eyes with STGD, and 28 control eyes. Main outcome measures were the mean superficial (FAZ-S; mm2 ) and deep foveal avascular zone (FAZ-D; mm2 ) measured with OCTA as well as the mean arterial (A-SO2 ; %), venular (V-SO2 ; %) oxygen saturation, their difference (A-V SO2 ; %) and the corresponding mean diameters of the peripapillary retinal arterioles (D-A; µm) and venules (D-V; µm) determined with RO. RESULTS: Stargardt disease (STGD) patients differed from controls and no-ME-RP by an enlarged FAZ-S and reduced A-SO2 and V-SO2 (p ≤ 0.013). No-ME-RP eyes presented with attenuated vessels (p < 0.001) and increased A-SO2 and V-SO2 (p ≤ 0.012) compared to controls and STGD. The FAZ-D showed significant interactions with A-SO2 (p = 0.003) in no-ME-RP while the FAZ-S correlated with visual acuity in no-ME-RP (p = 0.007) and STGD (p = 0.034). CONCLUSION: Retinitis pigmentosa (RP) and Stargardt disease (STGD) patients suffer from microvascular and metabolic alterations, however, showing a different pattern. A combined microvascular-metabolic model may therefore allow to more precisely characterize RP and STGD as well as presumably other inherited retinal diseases.

Functional and structural outcome after vitrectomy combined with subretinal rtPA Injection with or without additional intravitreal Bevacizumab injection for submacular hemorrhages.

BACKGROUND: To analyze the functional and anatomical outcome after vitrectomy with subretinal rtPA (recombinant tissue plasminogen activator) combined with or without an intravitreal Bevacizumab injection. PATIENTS AND METHODS: Retrospective, consecutive case series of 31 pseudophakic patients with submacular hemorrhage (SMH) due to neovascular age-related macular degeneration (AMD) treated with vitrectomy, subretinal rtPA and pneumatic air displacement with or without an additional intravitreal Bevacizumab injection. The primary endpoints were best-corrected visual acuity (BCVA), and central macular thickness (CMT) measured by SD­OCT. The secondary endpoint was a displacement of hemorrhage from the subretinal space three months after surgery. RESULTS: 31 eyes of 31 patients were treated with vitrectomy and subretinal rtPA. 17/31 were treated simultaneously with an intravitreal Bevacizumab injection (group +B) and 14/31 without (group -B). The mean visual acuity improved significantly in both groups (from 1.37±0.39 to 1.03±0.57 logMAR in +B and from 1.48±0.48 to 1.01±0.38 logMAR in group -B, p<0.05). The mean CMT decreased in group +B from 607±179 µm to 424±205 µm (p = 0.2) and in group -B from 722±216 µm to 460±202 µm (p<0.05). A central displacement of the hemorrhage could be achieved in 47% in group +B, whereas in group -B displacement could be achieved in 50% (p = 0.44). CONCLUSIONS: Vitrectomy with subretinal rtPA injection and air tamponade with or without simultaneous intravitreal Bevacizumab injection displaces SMH and improves BCVA effectively. In comparison, the postoperative outcome is comparable regardless of whether or not intravitreal bevacizumab is applied simultaneously.

Retinal vessel oximetry in children with inherited retinal diseases.

BACKGROUND: Retinal vessel oximetry (RO) has been used to show altered metabolic function in patients with inherited retinal diseases (IRDs). The aim of this study was to investigate RO parameters of children with IRDs and presumed IRD carriers (pIRDc) and to compare them to controls. METHODS: In this cross-sectional cohort study, 142 eyes from 71 Caucasian subjects were included: 40 eyes with IRDs, 26 eyes with pIRDc and 76 control eyes. The oxygen saturation was measured with the Retinal Vessel Analyser (IMEDOS Systems UG, Jena, Germany). Mean oxygen saturations in the peripapillary retinal arterioles (A-SO2 ; %) and venules (V-SO2 ; %) were estimated, and their difference (A-V SO2 ; %) was calculated. In addition, we evaluated the mean diameter in all major retinal arterioles (D-A; µm) and venules (D-V; µm). anova-based linear mixed-effects models were calculated with SPSS® . RESULTS: In general, children suffering from IRDs differed from controls when the A-SO2 and A-V SO2 were taken into account: both the A-SO2 and the A-V SO2 were significantly increased (p = 0.012). In subgroup analyses, children suffering from rod-cone dystrophy (RCD) presented an A-SO2 increase (99.12 ± 8.24%) when compared to controls (91.33 ± 10.34%, p = 0.014) and pIRDc (92.37 ± 6.57%, p = 0.065). For V-SO2 significant changes in RCD (67.42 ± 9.19%) were found in comparison with controls (58.24 ± 11.74%, p < 0.041), pIRDc (56.67 ± 7.16%, p = 0.007), cone-rod dystrophies (CRD, 52.17 ± 5.32%, p < 0.001) and inherited macular dystrophies (IMD, 55.74 ± 6.96%, p = 0.004), In addition, A-V SO2 was decreased in RCD (31.69 ± 3.92%) when measured against CRD (41.9 ± 8.87%, p = 0.017) or IMD (39.52 ± 8.95%, p = 0.059). CONCLUSION: In general, we found that children with IRDs presented early metabolic changes. Within IRDs, children with RCD showed more affected metabolic changes. Thus, RO may support early screening to rule out IRDs in children, and more precisely may help to differentiate those suffering from RCD.

The impact of macular edema on microvascular and metabolic alterations in retinitis pigmentosa.

PURPOSE: The primary aim of our study was to evaluate retinal microvascular anomalies recorded with optical coherence tomography angiography (OCTA) and the retinal metabolic function measured with retinal oximetry (RO) in patients with retinitis pigmentosa (RP). The secondary aim of the study was to link the presence of macular edema to microvascular and metabolic parameters in RP. METHODS: OCTA and RO were performed on 94 eyes: 64 eyes diagnosed with RP with (ME-RP) and without (no-ME-RP) macular edema were compared with 30 control eyes. Study end points were as follows: mean superficial (FAZ-S) and deep foveal avascular zone (FAZ-D) determined by OCTA. In addition, we evaluated the mean arterial (A-SO2; %), venular (V-SO2; %) oxygen saturation, their difference (A-V SO2; %), as well as the corresponding mean diameter of the retinal arterioles (D-A; µm) and venules (D-V; µm). RESULTS: RP patients differed from controls by enlarged FAZ-S and FAZ-D (p ≤ 0.001), attenuated retinal vessels (p ≤ 0.001), and increased retinal vessel oxygen saturation (p ≤ 0.010). Subgroup analyses within RP patients revealed more pronounced alterations of microvascular parameters and metabolic function in the presence of macular edema. In the no-ME-RP subgroup, significant interactions were present between FAZ-S, A-SO2, and V-SO2, whereas in the ME-RP subgroup, we found significant correlations between FAZ-D and D-A. CONCLUSION: A combined microvascular structure-metabolic function approach enhances our understanding of inherited retinal diseases. The presence of macular edema in RP seems to be a result of more altered microvascular-metabolic function. Macular edema should thus be taken into consideration when evaluating microvascular and/or metabolic changes in RP.

Optical coherence tomography angiography findings in patients undergoing transcorneal electrical stimulation for treating retinitis pigmentosa.

PURPOSE: Transcorneal electrical stimulation (TES) is a novel treatment approach for patients with retinitis pigmentosa (RP). The aim of our study was to observe changes in optical coherence tomography angiography (OCTA) that would be attributed to TES treatment. METHODS: A total of 73 eyes were included: 43 eyes of 22 subjects (11 ♀, 11 ♂) suffering from RP were examined at baseline (BL), after first stimulation (TS), 1 week (1W), and 6 months (6M) after treatment initiation and were compared with 30 control eyes of 15 subjects (8 ♀, 7 ♂). TES was performed simultaneously on both eyes for 30 min weekly. OCTA scans of 9 × 15 mm were recorded with a PLEX Elite 9000 swept-source OCTA device (Carl Zeiss Meditec AG, Jena). Vascular density metrics such as perfusion density (PD) and vessel density (VD) were calculated automatically for the macular area by using standardised extended early treatment diabetic retinopathy study (ETDRS) grids centred around the fovea. In addition, the capillary perfusion density (CPD) and the capillary flux index (CFI) of the peripapillary nerve fibre layer microvasculature in all four quadrants of an annulus centred at the optic disc were measured. All parameters were determined over all retinal layers and separately for the superficial (SCP) and deep capillary plexus (DCP). ANOVA-based linear mixed-effects models were calculated with SPSS®. RESULTS: Throughout the course of TES treatment, the macular VD and PD of all retinal layers in all subsections showed a slight decrement without reaching statistical significance, also when analysed separately in the SCP and DCP (p > 0.08). In analogy, the average CPD and CFI also presented with a slight decrement (p > 0.20). However, when compared with controls, most OCTA parameters showed a significant decrement (p < 0.05). When analysed systematically in all subsections of the extended ETDRS grid, the temporal macular subsections within the outer ring (radius 1.5-3 mm) and also of the peripheral C1, C2, and C3 rings (radius 3-7.5 mm) showed lower VD and PD values when compared with the other subsections (p < 0.05). CONCLUSION: Vascular density metrics in the macular region and the peripapillary microvasculature appear to remain unaffected by continuous TES treatment within a period of 6 months.

New Technologies for Outcome Measures in Glaucoma: Review by the European Vision Institute Special Interest Focus Group.

Glaucoma is the leading cause of irreversible blindness worldwide, with an increasing prevalence. The complexity of the disease has been a major challenge in moving the field forward with regard to both pathophysiological insight and treatment. In this context, discussing possible outcome measures in glaucoma trials is of utmost importance and clinical relevance. A recent meeting of the European Vision Institute (EVI) special interest focus group was held on "New Technologies for Outcome Measures in Retina and Glaucoma," addressing both functional and structural outcomes, as well as translational hot topics in glaucoma and retina research. In conjunction with the published literature, this review summarizes the meeting focusing on glaucoma.

Influence of cataract light scatters on retinal vessel oxygen saturation.

BACKGROUND: The aim of our study was to compare metabolic (oxygen saturation; %) and anatomical parameters (retinal vessel diameter; µm) of retinal vessel oximetry (RO) in patients with cataract formation against those of healthy controls with clear lenses. METHODS: A total of 96 eyes of 62 subjects were examined: 51 eyes from 33 cataract patients (mean age: 64.8y) were compared to 45 eyes from 29 controls with clear lenses (mean age: 61.5y). RO was performed with the oxygen saturation measurement tool from the RVA (IMEDOS Systems UG). The oxygen saturation in all major peripapillary retinal arterioles (A-SO2 ) and venules (V-SO2 ) was measured, and their difference (A-V SO2 ) was calculated. In addition, the corresponding diameter in retinal arterioles (D-A) and venules (D-V) was evaluated. Cataract formation was graded according to the Lens Opacities Classification System III (LOCS III). Oximetry data were compared with the grade of cataract formation within both groups. For statistical evaluation, anova-based linear mixed-effects models were calculated (spss® , pairwise comparisons: Bonferroni-corrected; p < 0.05). RESULTS: Cataract eyes showed significantly lower A-SO2 and A-V SO2 values (mean ± SD 92.52 ± 9.80% and 28.56 ± 9.80%), when compared to healthy controls (95.47 ± 4.48% and 34.8 ± 7.08%; p = 0.046 and p = 0.001). Within the cataract group, cortical opacities showed significant interactions with the A-SO2 , V-SO2 and the A-V SO2 parameters (p = 0.027; p = 0.002; and p = 0.026, respectively). CONCLUSIONS: These data indicate that the cataract-induced light scatter influences optical retinal oxygen measurements. Cortical opacities showed the highest influence on RO measurement when compared to nuclear opacification, nuclear colour and posterior cataract formation.

New Technologies for Outcome Measures in Retinal Disease: Review from the European Vision Institute Special Interest Focus Group.

Novel diagnostic tools to measure retinal function and structure are rapidly being developed and introduced into clinical use. Opportunities exist to use these informative and robust measures as endpoints for clinical trials to determine efficacy and to monitor safety of therapeutic interventions. In order to inform researchers and clinician-scientists about these new diagnostic tools, a workshop was organized by the European Vision Institute. Invited speakers highlighted the recent advances in state-of-the-art technologies for outcome measures in the field of retina. This review highlights the workshop's presentations in the context of published literature.

Metabolic monitoring of transcorneal electrical stimulation in retinitis pigmentosa.

PURPOSE: Transcorneal electrical stimulation (TES) is a novel treatment approach for patients with retinitis pigmentosa (RP). With progression of RP, loss of photoreceptors leads to less oxygen consumption and lower demand in the retina. Retinal oximetry (RO), as a non-invasive method to analyse oxygen saturation in retinal vessels, promises to be a useful therapy monitoring tool. The aim of our study was to observe changes in RO that would be attributed to therapeutic intervention. METHODS: A total of 43 eyes of 22 subjects (11♀ 11♂) suffering from RP were examined at baseline, after the first stimulation, 1 week and 6 months after TES (OkuStim®). Stimulation was performed for 30 min weekly at 200% of the individual phosphene threshold, simultaneously on both eyes. The oxygen saturation was examined at baseline and following TES stimulation with the oxygen saturation tool of the Retinal Vessel Analyser (RVA; IMEDOS Systems UG, Jena, Germany). The global oxygen saturation parameters (in %), within 1.0-1.5 optic disc diameters from the disc margin, in retinal arterioles (A-SO2) and venules (V-SO2) were estimated and their difference (A-V SO2) was calculated. In addition, we evaluated the diameters (in µm) in the corresponding arterioles (D-A) and venules (D-V). ANOVA-based linear mixed-effects models were calculated with SPSS®. RESULTS: Six months after TES treatment, the mean A-SO2 increased (from 96.48 ± 12.27 to 100.15 ± 5.56%, p = 0.09), while the V-SO2 decreased (from 61.61 ± 12.78 to 59.79 ± 11.15%, p = 0.48). The A-V SO2, which represents the oxygen consumption of the retina, showed a statistically significant increase from 34.87 ± 9.38% at baseline to 41.36 ± 9.18% after 6 months (p = 0.02). TES had no influence on the D-A and D-V (p > 0.6). CONCLUSION: These data indicate that TES therapy in RP leads to an increased oxygen consumption of the retina. RO may thus serve as a sensitive monitoring method for TES therapy in RP.

[Long-term Follow-up After Cryocoagulation in Preterm Newborns from Northern Greece with Retinopathy of Prematurity: Three Year Results]. / Langzeit-Follow-up nach Exokryokoagulation bei Frühgeborenenretinopathie in Nordgriechenland: 3-Jahres-Ergebnisse.

BACKGROUND: This is a retrospective study of the efficacy of treatment of neonates (NN) with exocryocoagulation retinopathy of prematurity (ROP) with respect to morphology of the retina and visual function. MATERIALS AND METHODS: Out of a total of 3103 neonates, 304 (9.8%) had a ROP. 66 of these were treated. All neonates were observed for 3 years after this treatment. When the patients suffered retinal ablation or dragging of the macula, the treatment was rated as unsuccessful. Best corrected grid visual acuity and best corrected visual acuity were assessed with Lea symbols and Kay pictures. RESULTS: The 66 treated neonates (132 eyes) had a gestation age of less than 28 weeks and weight at birth of < 1280 g. 28 neonates exhibited ROP and the rest in zone 2. Among these 66 neonates, 64 (128 eyes) exhibited improved vision. 37 neonates (74 eyes) also exhibited morphological improvement. Only one neonate developed retinal detachment. CONCLUSION: Early treatment with cryopexia of neonates with ROP can improve vision and stabilise the retina.