The Presence of Hyperreflective Foci Reflects Vascular, Morphologic and Metabolic Alterations in Retinitis Pigmentosa.

BACKGROUND: The presence of hyperreflective foci (HRF) in retinitis pigmentosa (RP) is a potentially new finding. We investigated the presence of HRF in SD-OCT images in eyes with RP and its relation to vascular, morphologic and metabolic findings in RP. METHODS: The study was performed on 42 RP patients and 24 controls. Using SD-OCT, we calculated the amount of HRF within the entire retina (HRF-ER) and the outer nuclear layer (HRF-ONL). Retinal vessel diameters (µm) and oxygen saturation (%) values were measured using Oxymap T1. We evaluated the mean diameter in retinal arterioles (D-A) and venules (D-V), the corresponding oxygen saturation values (A-SO2, V-SO2) and the oxygen saturation difference (A-V SO2). RESULTS: RP differed from controls by HRF-ER, HRF-ON and EZ-length (p < 0.001). D-A and D-V were narrower and A-SO2 and V-SO2 were higher in RP (p ≤ 0.001). Within RP, significant interactions were found between the HRF-ER* group and: BCVA, EZ length, D-A, A-SO2 and A-V SO2 (p ≤ 0.018). The HRF-ONL* group interactions were significant for: BCVA, EZ length, D-A, A-SO2 and A-V SO2 (p ≤ 0.014). CONCLUSION: The present study highlights the presence of HRF to reflect the vascular, morphologic and metabolic alterations in RP. These biomarkers seem to be associated with remodeling and apoptosis that occur with the progression of degeneration.

Peripapillary Oxygenation and Retinal Vascular Responsiveness to Flicker Light in Primary Open Angle Glaucoma.

The aim of our study was to evaluate peripapillary oxygenation and its relationship to retinal vascular responsiveness to flicker light in patients with primary open angle glaucoma (POAG). Retinal vessel oxygen saturation was measured in 46 eyes of 34 Caucasian patients with POAG and in 21 eyes of 17 age-matched controls using the oximetry tool of Retinal Vessel Analyser (RVA: IMEDOS Systems UG, Jena, Germany). The mean oxygen saturation of the major arterioles (A-SO2; %) and venules (V-SO2; %), as well as the corresponding arterio−venular difference (A-V SO2; %), were calculated. We also measured retinal vascular responsiveness (RVR) to flicker light by means of RVA. Glaucoma patients were divided in two subgroups according to their median arteriolar and venular vascular responsiveness to flicker light (AFR and VFR). Glaucomatous damage was assessed by optical coherence tomography (Carl Zeiss Meditec, Dublin, CA, USA) and static automated perimetry (Octopus, program G2/standard strategy: Haag-Streit International, Köniz, Switzerland). In addition, we calculated the mean peripapillary oxygen exposure [ppO2E; %/µm] by dividing the mean A-V SO2 with the mean retinal nerve fibre layer (RNFL) thickness. In glaucoma patients, A-SO2 and V-SO2 values were significantly increased, and their difference decreased when compared to controls (p < 0.017; linear mixed-effects model). Grouped with respect to retinal vascular responsiveness to flicker light, subjects with reduced VFR (≤2.9%) had significantly higher ppO2E (0.49 ± 0.08%/µm, respectively, 0.43 ± 0.06%/µm; p = 0.027). Additionally, higher ppO2E in glaucoma patients correlated negatively with the neuroretinal rim area (p < 0.001) and the RNFL thickness (p = 0.017), and positively with the mean defect of the visual field (p = 0.012). Reduced venular vascular responsiveness in our glaucoma patients was associated with increased peripapillary oxygenation exposure. Thus, ganglion cells and their axons in glaucomatous eyes with reduced retinal vascular responsiveness are prone to be more exposed to higher oxidative stress, probably contributing to the further progression of glaucomatous damage.

Structural, Microvascular, and Functional Findings Associated with Fovea Plana.

PURPOSE: To analyse structural (OCT), microvascular (OCTA), and functional changes (BCVA, mfERG) associated with fovea plana and to compare it to healthy controls. METHODS: A retrospective observational study was performed on 13 patients (26 eyes; aged 34.46 y ± 20.26) with a clinical picture of fovea plana and 15 controls (30 eyes; aged: 41.47 y ± 14.03). RESULTS: In fovea plana, BCVA ranged from 0.25 to 1.0, with a spherical error of - 5.5 to + 18.0 dpt. Posterior segment changes included elevated papillomacular retinal fold, uveal effusion syndrome, crowded optic discs, and hypopigmented fundus. OCTA imaging of the superficial (FAZ-S), intermediate (FAZ-I), and deep foveal avascular zone (FAZ-D) confirmed absence of foveal avascular zone (FAZ-S in 13 eyes, FAZ-I in 21 eyes, and FAZ-D in 10 eyes). Fovea plana patients had a significantly smaller FAZ-S, FAZ-I, and FAZ-D than controls (p < 0.001). Within the fovea plana group, a smaller FAZ-S correlated with reduced BCVA (p = 0.004) and with reduced mfERGs in zones 1 and 2 (p = 0.001 and p = 0.017). Also, a smaller FAZ-D showed positive correlations with the mfERG, with statistically significant values in zones 1 and 2 (p = 0.003 and p = 0.017). CONCLUSION: In conclusion, our results confirm an altered structural, microvascular, and functional pattern in patients with a clinical picture of fovea plana. As documented by the functional microvascular interactions in our study, the developmental arrest in foveation reflects the functional maturation by means of visual acuity and central retinal function.

Microvascular abnormalities and long-term efficacy after stereotactic radiotherapy under continued intravitreal anti-VEGF treatment for neovascular AMD.

BACKGROUND: For treatment of neovascular age-related macular degeneration (nAMD), multiple intravitreal injections of drugs targeting vascular endothelial growth factors (VEGF) result in a high burden for patients and healthcare systems. Low-energy stereotactic radiotherapy (SRT) might reduce the anti-VEGF need. This study evaluated the long-term efficacy and safety of adjunct SRT to anti-VEGF injections in a treat-and-extend regimen in nAMD. METHODS: 50 consecutive patients were followed 3 years after single-session SRT, a safety analysis including standardised study imaging, and a reading centre based image analysis was performed after 2 years. RESULTS: After increase from baseline (4.24±0.66 weeks) to 12 months (7.52±3.05 weeks, p<0.001), mean recurrence-free anti-VEGF treatment interval remained stable at 24 (7.40±3.17, p=0.746) and 36 months (6.89±3.00, p=0.175). Mean visual acuity change was -5.8±15.9 and -11.0±20.1 letters at 24 and 36 months, respectively. 36% of eyes showed microvascular abnormalities (MVAs) on colour fundus photography and/or fluoresceine angiography most frequently located in parafoveal inferior and nasal regions. CONCLUSION: In real life, low-energy SRT was associated with a reduced anti-VEGF injection frequency through year 3. However, due to an observed visual acuity reduction and remarkable number of MVAs, a close follow-up of these patients is recommended. The real-life use, optimal treatment schedule and dose should be rediscussed critically.

Peripapillary and macular microvasculature in neovascular age-related macular degeneration in long-term and recently started anti-VEGF therapy versus healthy controls.

Aim: To investigate the peripapillary and macular microvasculature in neovascular age-related macular degeneration (nAMD) in recently started versus long-term anti-vascular endothelial growth factor (VEGF) therapy and healthy controls. Methods: Eyes with nAMD treated in a treat-and-extend regimen were assigned to group 1 (<5 injections) or 2 (≥20 injections) whereas group 3 constituted the healthy age-matched controls. Blood flow signals were acquired using PLEX® Elite 9000 swept-source optical coherence tomography angiography (OCTA) of the macular and peripapillary regions. Mean ganglion cell complex (GCC) thickness values were quantified using spectral-domain optical coherence tomography (SD-OCT). Results: Including 80 eyes whereof 40 controls, macular superficial perfusion density was significantly reduced in group 1 and 2 compared to controls (p < 0.001; p = 0.010) without a difference between groups 1 and 2. Peripapillary perfusion parameters did not correlate with post-operative intraocular pressure (IOP) or number of anti-VEGF injections. Mean peripapillary flux index was significantly lower in group 2 than in controls (p = 0.023) and significantly decreased in the nasal quadrants for both AMD groups compared to group 3 (p = 0.013; p < 0.001). Mean peripapillary perfusion density was significantly reduced in both AMD groups compared to controls (0.515 ± 0.02 versus 0.556 ± 0.03, p < 0.0001). Conclusion: Frequency of anti-VEGF treatment in nAMD and post-operative IOP showed no correlation with peripapillary perfusion parameters, but anti-VEGF treated nAMD patients exhibited partly altered peripapillary perfusion compared to healthy controls. Reduced macular perfusion density of the inner retina in anti-VEGF treated nAMD compared to healthy controls might be discussed as an anti-VEGF treatment effect or a characteristic of nAMD.

Retinal Oxygenation in Inherited Diseases of the Retina.

(1) Background: The aim of our study was to investigate the relationship between retinal metabolic alterations (retinal vessel oximetry, RO) and structural findings (retinal vessel diameter, central retinal thickness and retinal nerve fiber layer thickness, RNFL) in patients with inherited retinal diseases (IRDs). (2) Methods: A total of 181 eyes of 92 subjects were examined: 121 eyes of 62 patients with IRDs were compared to 60 eyes of 30 healthy age-matched controls. The retinal vessel oximetry was performed with the oxygen saturation measurement tool of the Retinal Vessel Analyser (RVA; IMEDOS Systems UG, Jena, Germany). The oxygen saturation in all four major peripapillary retinal arterioles (A-SO2; %) and venules (V-SO2; %) were measured and their difference (A-V SO2; %) was calculated. Additionally, retinal vessel diameters of the corresponding arterioles (D-A; µm) and venules (D-V; µm) were determined. The peripapillary central retinal thickness and the RNFL thickness were measured using spectral domain optical coherence tomography (SD-OCT) (Carl Zeiss Meditec, Dublin, CA, USA). Moreover, we calculated the mean central retinal oxygen exposure (cO2-E; %/µm) and the mean peripapillary oxygen exposure (pO2-E; %/µm) per micron of central retinal thickness and nerve fiber layer thickness by dividing the mean central retinal thickness (CRT) and the RNFL thickness with the mean A-V SO2. (3) Results: Rod-cone dystrophy patients had the highest V-SO2 and A-SO2, the lowest A-V SO2, the narrowest D-A and D-V and the thickest RNFL, when compared not only to controls (p ≤ 0.040), but also to patients with other IRDs. Furthermore, in rod-cone dystrophies the cO2-E and the pO2-E were higher in comparison to controls and to patients with other IRDs (p ≤ 0.005). Cone-rod dystrophy patients had the lowest cO2-E compared to controls and patients with other IRDs (p ≤ 0.035). Evaluated in central zones, the cO2-E was significantly different when comparing cone-rod dystrophy (CRD) against rod-cone dystrophy (RCD) patients in all zones (p < 0.001), whereas compared with controls and patients with inherited macular dystrophy this was observed only in zones 1 and 2 (p ≤ 0.018). The oxygen exposure was also the highest in the RCD group for both the nasal and the temporal peripapillary area, among all the evaluated groups (p ≤ 0.025). (4) Conclusions: The presented metabolic-structural approach enhances our understanding of inherited photoreceptor degenerations. Clearly demonstrated through the O2-E comparisons, the central and the peripapillary retina in rod-cone dystrophy eyes consume less oxygen than the control-eyes and eyes with other IRDs. Rod-cone dystrophy eyes seem to be proportionally more exposed to oxygen, the later presumably leading to more pronounced oxidative damage-related remodeling.

Predictors for 2-Year Functional and Morphological Outcomes of a Treat-and-Extend Regimen with Ranibizumab in Patients with Diabetic Macular Edema.

PURPOSE: The purpose of the study was to investigate longer term functional and morphological outcomes and their predictors in diabetic macular edema (DME) following a treat-and-extend regimen (TER) without loading dose under ranibizumab. METHODS: Patient data were reviewed and analyzed retrospectively over a period of 24 months after initiation of TER. Best-corrected visual acuity (BCVA), treatment frequency, and quantitative and qualitative spectral-domain optical coherence tomography parameters were assessed. RESULTS: 118 eyes of 87 patients were included. A mean of 9.74 ± 2.13 injections in the first and 7.63 ± 2.29 in the second year were applied. There were significant gains of BCVA and reductions in central retinal thickness from baseline to 12 and 24 months (all p < 0.001). Percentage of eyes with an intact inner segment/outer segment (IS/OS) junction increased from 15.3% at baseline to 42.1% at 24 months (p < 0.001). An intact IS/OS junction at baseline increased the probability of having a dry retina after 12 months by 79.3% (p = 0.017) and after 24 months by 88.1% (p = 0.040). Less IS/OS disruption at baseline predicted longer maximum recurrence-free treatment intervals at 2 years (r = -0.345, p < 0.001) and better BCVA at 1 year (r = -0.347, p < 0.001). Baseline bigger intraretinal cysts were associated with more IS/OS disruption at 24 months (r = 0.305, p = 0.007). Younger age and lower BCVA at baseline were predictive for a higher BCVA gain at 24 months (p = 0.046, p < 0.001). CONCLUSION: Ranibizumab applied in a TER without loading dose in DME significantly improves visual acuity and retinal anatomical structure throughout 2 years. The evaluated predictors might help guide routine clinical treatment in DME.

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.

Normative values of retinal vessel oximetry in healthy children against adults.

BACKGROUND: Retinal oximetry (RO) has been established as a non-invasive method to analyse oxygen saturation in retinal vessels. The aim of our study was to compare the RO parameters of healthy children to those in adults. METHODS: A total of 200 eyes of 104 healthy subjects were examined: 20 eyes of children aged <10 years and 62 eyes of children aged 10-19 years were compared to the eyes of adult controls from five different age groups (20-29 years:n = 24; 30-39 years:n = 32; 40-49 years:n = 15; 50-59 years:n = 20, 60-80 years:n = 27; n indicates the number of analysed eyes). The oxygen saturation was estimated with the oxygen saturation measurement tool of the Retinal Vessel Analyser (RVA; IMEDOS Systems UG, Jena, Germany). The global oxygen saturations, within 1.0-1.5 optic disc diameters from the disc margin, 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 four major retinal arterioles (D-A; µm) and venules (D-V; µm). The ratio between venular and arterial vessel diameter (D-V/A; µm) was calculated thereafter. For statistical evaluation, anova-based linear mixed-effects models were calculated with spss® . RESULTS: Based on our results, younger children (<10 years) present a statistically significant lower A-SO2 and A-V SO2 when compared to adult subgroups. The D-A values revealed to be significantly lower in 10 + children when compared to the other groups, while the D-V values did not show significant differences. CONCLUSION: These data indicate that the retinal oxygen metabolism changes throughout lifetime. Therefore, normative data for different age groups are mandatory.

The effect of autoimmune retinopathy on retinal vessel oxygen saturation.

PURPOSE: To study the retinal vessel oxygen saturation alterations in patients with autoimmune retinopathy (AIR) and patients with autoimmune retinopathy associated with retinitis pigmentosa (AIR-RP) in comparison with healthy controls and patients with isolated retinitis pigmentosa (RP). DESIGN: Prospective, cross-sectional, and non-interventional study. SUBJECTS: Retinal vessel oximetry (RO) was performed on a total of 139 eyes: six eyes suffering from AIR and four eyes with AIR-RP were compared to 59 healthy control eyes and to 70 eyes with RP. METHODS: A computer-based program of the retinal vessel analyser unit (IMEDOS Systems UG, Jena, Germany) was used to evaluate retinal vessel oxygen saturation. The mean oxygen saturation in the first and second branch retinal arterioles (A-SO2) and venules (V-SO2) were measured and their difference (A-V SO2) was calculated. In addition, we measured the diameter of the retinal arterioles (D-A) and venules (D-V). MAIN OUTCOME MEASURES: Oxygen metabolism is altered in patients with isolated AIR and AIR-RP. RESULTS: Both, AIR and AIR-RP groups, differed from healthy controls showing significantly higher V-SO2 values and significantly lower A-V SO2 values (p < 0.025). In addition, the AIR-RP group could be differentiated from eyes suffering from isolated RP by means of significantly higher V-SO2 values. Comparing retinal vessel diameters, both, the AIR and AIR-RP groups, presented with significant arterial (p = 0.05) and venular (p < 0.03) vessel attenuation than the healthy control group. CONCLUSIONS: Based on our results, in analogy to patients suffering from RP, oxygen metabolism seems to be altered in AIR patients.

Higher retinal vessel oxygen saturation: investigating its relationship with macular oedema in retinitis pigmentosa patients.

PURPOSE: Primary objective-to investigate the effect of retinal vessel oxygen saturation (SO2) on macular oedema (ME) in retinitis pigmentosa (RP) patients. Secondary objective-to link the presence of ME to metabolic (oxygen saturation of retinal vessels, SO2), functional (multifocal electroretinography, mfERG) and structural (Spectral Domain Optical Coherent Tomography, SD-OCT) alterations in RP. DESIGN: Prospective, cross-sectional, non-interventional study. SUBJECTS: Patients with typical RP (N = 37) and controls (N = 19), who underwent retinal vessel Oximetry (RO), SD-OCT and mfERG, were included. METHODS: A computer-based program of the retinal vessel analyser unit (IMEDOS Systems UG, Jena, Germany) was used to measure SO2. We evaluated the mean SO2, in all major retinal arterioles (oxygen saturation in retinal arterioles, A-SO2, %) and venules (oxygen saturation in retinal venules, V-SO2, %). MfERG responses were averaged in zones (zone 1 (0-3°), zone 2 (3-8°) and zone 3 (8-15°)) and compared to corresponding areas of the OCT. The effect of ME on SO2 was evaluated dividing the RP in two subgroups: with clinical appearance of ME (ME-RP) and without it (no-ME-RP). MAIN OUTCOME MEASURES: Parallel recording and juxtaposition of metabolic (SO2) to structural (OCT) and functional-(mfERG) measures. Mean ( ± SD) A-SO2 and V-SO2 were higher in no-ME-RP (96.77% (±6.31) and 59.93% (±7.76)) and even higher in the ME-RP (99.82% (±6.21) and 65.63% (±7.63)), compared to controls (93.15% (±3.76) and 53.77% (±3.70), p ≤ 0.006). RESULTS: The subgroup ME-RP differed significantly from the subgroup no-ME-RP by increased A-SO2 and V-SO2, p ≤ 0.026. The presence of ME confirmed a different relationship between the altered SO2 and the vessel diameters, against the functional and structural parameters. CONCLUSION: Based on our results, the presence of macular oedema indicates a tendency toward greater alteration of the metabolic function in RP patients.

Spectral-Domain Optical Coherence Tomography-Driven Treat-and-Extend and Pro Re Nata Regimen in Patients with Macular Oedema due to Retinal Vein Occlusion: 24-Month Evaluation and Outcome Predictors.

PURPOSE: To analyse the efficacy and outcome predictors of ranibizumab using a spectral-domain optical coherence tomography (SD-OCT)-driven treat-and-extend regimen (TER) versus SD-OCT-driven pro re nata regimen (PRN) in patients with cystoid macular oedema (CME) due to branch or central retinal vein occlusion (BRVO, CRVO). METHODS: Retrospective, consecutive case series. Evaluation included best corrected visual acuity (BCVA), morphological parameters on SD-OCT, and treatment frequency. RESULTS: From baseline to months 12, 18, and 24, BCVA improved by 16.6 ± 13.1, 15.5 ± 14.4, and 16.6 ± 15.8 letters, respectively, in TER (n = 45), compared to 11.3 ± 17.0, 11.0 ± 15.0, and 10 ± 20.5 letters in PRN (n = 31) (p = 0.152, p = 0.237, p = 0.172). The mean reduction in central retinal thickness was -261 ± 189, -272 ± 188, and -264 ± 158 µm, respectively, in TER, compared to -130 ± 196, -140 ± 210, and -166 ± 207 µm in PRN (p = 0.006, p = 0.017, p = 0.064). 59% (53%) of TER and 22% (17%) of PRN patients showed no intra- or subretinal fluid on SD-OCT at 12 (24) months. Using TER, the maximum recurrence-free treatment interval increased from 8.9 ± 2.3 weeks at 12 months to 9.8 ± 2.3 and 10.5 ± 2.7 weeks at 18 and 24 months, respectively. The number of injections was significantly higher in the TER than in the PRN group. CONCLUSIONS: In CME, due to BRVO/CRVO, TER provides better morphological outcome using more injections than PRN.

Low-Energy Stereotactic Radiotherapy for Treatment of Exudative Age-Related Macular Degeneration in a Treat-and-Extend Regimen.

BACKGROUND AND OBJECTIVE: To evaluate the effectiveness and safety of low-energy stereotactic radiotherapy (SRT) combined with anti-vascular endothelial growth factor (VEGF) treatment following a treat-and-extend regimen (TER) in wet age-related macular degeneration (AMD). PATIENTS AND METHODS: Before/after SRT, the authors compared retrospective consecutive case series of 50 patients requiring frequent anti-VEGF treatment (every 4 or 6 weeks) in wet AMD, treated with a single session of SRT and TER (same manner pre/post-SRT). Outcomes were visual acuity (VA), recurrence-free interval, and central retinal thickness (CRT). RESULTS: After SRT, CRT was reduced from baseline (407.3 µm ± 153.2 µm) to 12 months (320.2 µm ± 112.1 µm; P < .001), with statistical significance from month 2 onward. VA was stable for 12 months (64.0 letters ± 15.1 letters vs. 63.6 letters ± 16.2 letters). The mean recurrence-free interval increased from 4.24 weeks ± 0.66 weeks to 7.52 weeks ± 3.05 weeks at 12 months (P < .001). No severe side effects were observed. CONCLUSION: Low-energy SRT, combined with anti-VEGF TER, was associated with reduced injection frequency and preserved VA during 12 months of follow-up. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:86-93.].

Baseline Optical Coherence Tomography Findings as Outcome Predictors after Switching from Ranibizumab to Aflibercept in Neovascular Age-Related Macular Degeneration following a Treat-and-Extend Regimen.

PURPOSE: To evaluate outcome predictors of aflibercept in neovascular age-related macular degeneration pretreated with ranibizumab based on a treat-and-extend regimen (TER). METHODS: We performed a retrospective evaluation of 18-month follow-up of 45 consecutive patients with limited response to ranibizumab. RESULTS: At month 18, mean central retinal thickness and intraretinal fluid (IRF) height were significantly reduced. The recurrence-free treatment interval (RFTI) increased from 7.0 ± 1.8 to 8.5 ± 2.4 weeks (p = 0.01); visual acuity remained stable. At month 18, 58.1% of patients showed a longer RFTI. At month 12, eyes with baseline subretinal fluid (SRF) had a shorter RFTI than those without SRF (p = 0.032). Eyes with baseline IRF showed a longer RFTI than those without IRF (p = 0.037). Baseline hyperreflective foci (HRF) presence indicated improvement in SRF (p = 0.024) and IRF at month 12 (p = 0.049). CONCLUSION: Baseline HRF presence predicted better morphological outcome, while SRF predicted a shorter RFTI and IRF a longer RFTI after switching from ranibizumab to aflibercept within a TER.

Reduced metabolic function and structural alterations in inherited retinal dystrophies: investigating the effect of peripapillary vessel oxygen saturation and vascular diameter on the retinal nerve fibre layer thickness.

PURPOSE: To evaluate the relationship between the peripapillary metabolic alterations [retinal vessel Oximetry (RO)] and the structural findings [retinal vessel diameter and retinal nerve fibre layer thickness (RNFL)] in patients with inherited retinal dystrophies (IRD). METHODS: Patients with IRD [24 patients with rod-cone dystrophy (RCD), 15 patients with cone-rod dystrophy, 13 patients with inherited maculopathy] and 18 age-matched controls, who underwent RO imaging and spectral domain optical coherence tomography, were included. The average and quadrant oxygen saturation in all four major peripapillary retinal arterioles (A-SO2 ) and venules (V-SO2 ) were measured, and their difference (A-V SO2 ) was calculated. The corresponding retinal vessel diameter of these arterioles (D-A) and venules (D-V) was measured. The data were compared to the peripapillary RNFL thickness within the IRD subgroups and to the data obtained in the controls. RESULTS: In general, patients with IRD had higher average V-SO2 values when compared to controls (p ≤ 0.029). Rod-cone dystrophy (RCD) patients differed from controls, but also from patients with other IRDs, when the average and quadrant oxygen saturation values (A-SO2 and V-SO2 ) were evaluated (p ≤ 0.026). Within the RCD group, the correlations of RNFL thickness to V-SO2 , A-V SO2 , D-A and D-V were significant (p ≤ 0.030), thus indicating a different relationship between the RNFL thickness and the examined parameters, when compared to the other groups. CONCLUSION: It becomes evident from our combined metabolic-structural approach that a prediction model, to identify which individual is at risk of developing a photoreceptor degeneration of RCD type, can be proposed. It will take into account the peripapillary retinal oxygen saturation, the retinal vessel diameter and the RNFL thickness values.

Metabolic and functional changes in retinitis pigmentosa: comparing retinal vessel oximetry to full-field electroretinography, electrooculogram and multifocal electroretinography.

PURPOSE: To determine a relationship between the retinal vessel saturation alterations and the residual retinal function measured by means of full-field electroretinography (full-field ERG), electrooculogram (EOG) and multifocal electroretinography (mfERG) in patients with retinitis pigmentosa (RP). METHODS: Retinal vessel oximetry (RO), full-field ERG, EOG and mfERG were performed on 43 eyes of 22 patients suffering from RP and were compared to those of 26 eyes of 13 healthy controls. The oxygen saturation in the first and second branch retinal arterioles (A-SO2 ) and venules (V-SO2 ) was measured, and their difference (A-V SO2 ) was calculated. Full-field ERG amplitudes, EOG parameters and averaged mfERG response amplitudes (within central 3°, between 3° and 8°, 8° and 15°, 15° and 24°) were evaluated in relation to the RO measurements. RESULTS: V-SO2 correlated negatively with the full-field ERG and EOG values, with increasing functional damage the V-SO2 was higher. The RP group was well distinguished from the controls when the RO measurements were correlated to the averaged N1 (baseline to trough), but also to the N1P1 (trough-to-peak) mfERG response amplitudes. Receiver operating characteristic (ROC) curve of V-SO2 , compared to those of N1 and N1P1 mfERG response averages (15-24°), presented a high differential margin between RP and controls (p < 0.001), shown by an area under the ROC curve of 0.912 (95% CI: 0.840-0.984). CONCLUSION: Retinal vessel saturation showed a significant relation to full-field ERG, EOG and mfERG. Thus, retinal vessel oximetry could potentially complement electrophysiological tests in monitoring disease progression in patients with RP.

Peripapillary retinal vessel diameter correlates with mfERG alterations in retinitis pigmentosa.

PURPOSE: To investigate relationship between the peripapillary retinal vessel diameter and the residual retinal function, measured by mfERG, in patients with retinitis pigmentosa (RP). PATIENTS AND METHODS: A cross-sectional study based on 23 patients with RP (43 eyes) and 20 controls (40 eyes) was performed. Retinal vessel diameters were measured using a computer-based program of the retinal vessel analyser (RVA; IMEDOS Systems UG, Jena, Germany). We evaluated the mean diameter in all four major retinal arterioles (D-A) and venules (D-V) within 1.0-1.5 optic disc diameters from the disc margin. The data were compared with the N1 amplitudes (measured from the baseline to the trough of the first negative wave), with the N1P1 amplitudes (measured from the trough of the first negative wave to the peak of the first positive wave) of the mfERG overall response and with the mfERG responses averaged in zones [zone 1 (0°-3°), zone 2 (3°-8°), zone 3 (8°-15°) and zone 4 (15°-24°)]. RESULTS: Mean (±SD) D-A and D-V were narrower in patients with RP [84.86 µm (±13.37 µm) and 103.35 µm (±13.65 µm), respectively] when compared to controls [92.81 µm (±11.49 µm) and 117.67 µm (±11.93 µm), respectively; the p-values between groups were p = 0.003 for D-A and p < 0.001 for D-V, linear mixed-effects model]. The RP group revealed clear differences compared to the controls: D-A and D-V became narrower with reduced mfERG responses. D-V correlated significantly with the overall mfERG N1 amplitudes (p = 0.013) and with N1P1 amplitudes (p = 0.016). D-V correlated with the mfERG amplitudes averaged in zones: (zone 2, 3 and 4; p ≤ 0.040) and N1P1 mfERG amplitudes (zones 1, 2, 3 and 4; p ≤ 0.013). CONCLUSIONS: Peripapillary retinal vessel diameter is reduced in RP proportionally to functional alterations.

Reproducibility of retinal oximetry measurements in healthy and diseased retinas.

PURPOSE: Retinal oximetry (RO) has been established as a non-invasive method to analyse oxygen saturation in retinal vessels. The aim of our study was to determine the reproducibility of RO images in healthy and in diseased retinas. METHODS: A total of 61 right eyes (244 RO images) in 61 subjects (35♀, 26♂) were examined: 22 controls, 18 patients with glaucoma and 21 patients with inherited retinal diseases (IRDs). Four test-retest RO images were obtained in each subject. Oxygen saturation was measured with the oxygen saturation measurement tool of the Retinal Vessel Analyser (RVA; IMEDOS Systems UG, Jena, Germany). The test-retest standard deviation within the subject's (±SDw ) measurements (the mean vessel oxygen saturation in retinal venules and arterioles), its coefficient of variation (CoV) and the intraclass correlation coefficients (ICC) were analysed. RESULTS: The average test-retest SDw in venules was ±2.52% (CoV = 4.35%) and in arterioles was ±1.67% (CoV = 1.76%). Among controls, glaucoma eyes and eyes with IRDs, the test-retest SDw in venules were ±2.33% (CoV = 4.48%), ±2.85% (CoV = 4.71%) and ±2.43% (CoV = 3.90%) (SDw p = 0.366 (CoV p = 0.452); one-way anova). The test-retest SDw in arterioles were ±1.65% (CoV = 1.80%), ±1.83% (CoV = 1.92%) and ±1.54% (CoV = 1.56%), respectively [SDw p = 0.762 (CoV p = 0.686)]. The ICCs in venules were 0.76 in controls, 0.69 in patients with glaucoma and 0.82 in patients with IRD. The ICCs in arterioles were, respectively, 0.92, 0.70 and 0.93. CONCLUSION: The reproducibility of RO in healthy, as well as in diseased retinas, is excellent. In the glaucoma group, the lower standard deviation between subjects (SDb ) for arterioles contributes to the lower ICCs. Nevertheless, the measurements of oxygen saturation in arterioles seem more reliable when compared to venules.

Retinal vessel oxygen saturation and its correlation with structural changes in retinitis pigmentosa.

PURPOSE: To study the influence of retinal structural changes on oxygen saturation in retinitis pigmentosa (RP) patients. METHODS: Oximetry measurements were performed on 21 eyes of 11 RP patients and compared to 24 eyes of 12 controls. Retinal oxygen saturation was measured in all major retinal arterioles (A-SO2) and venules (V-SO2) with an oximetry unit of the retinal vessel analyser (IMEDOS Systems UG, Jena, Germany). Oximetry data were compared with morphological changes measured by Cirrus optical coherence tomography (OCT) (Carl Zeiss Meditec, Dublin, CA, USA, macular thickness protocol). RESULTS: In RP patients, the retinal A-SO2 and V-SO2 levels were higher at 99.3% (p = 0.001, anova based on mixed-effects model) and 66.8% (p < 0.001), respectively, and the difference between the two (A-V SO2) was lower at 32.5% (p < 0.001), when compared to the control group (92.4%; 54.0%; 38.4%, respectively). With the RP group, the A-V SO2 correlated positively, not only with central macular thickness, but also with retinal thickness, in zones 2 and 3 (p = 0.006, p = 0.007, p = 0.014). CONCLUSION: These data indicate that oxygen metabolism was altered in RP patients. Based on our preliminary results, retinal vessel saturation correlated with structural alterations in RP. This method could be valuable in monitoring disease progression and evaluating a potential therapeutic response.

Effect of ageing on the retinal vascular responsiveness to flicker light in glaucoma patients and in ocular hypertension.

AIM: To evaluate the effect of ageing on the retinal vascular responsiveness to flicker light in glaucoma and ocular hypertension (OHT). METHODS: Retinal vascular response to flicker was measured with the retinal vessel analyser in 56 healthy subjects (59 ± 9 years), 50 primary open-angle glaucoma (POAG) (60 ± 10 years) and 46 OHT patients (62 ± 9 years). In the glaucoma group, the less damaged eye; in the OHT group, the eye with the higher intraocular pressure; and in healthy controls, one randomly selected eye was considered. Parametric and non-parametric linear regression analysis, as well as a model of covariance analysis (ANCOVA) was used to evaluate the effect of age on the vascular response. RESULTS: In all three groups (N=152) absolute (Pearson R: -0.19, p<0.019; Spearman R: -0.22, p<0.006) and relative change (Pearson R: -0.18, p<0.027; Spearman R: -0.21, p<0.010) were statistically associated with age. The ANCOVA showed no difference between the three groups in this regard (absolute change: p=0.43; relative change: p=0.51). CONCLUSIONS: Vascular responsiveness to flicker light decreases with age in healthy individuals, in glaucoma patients and in OHT patients. This effect seems to be comparable between the tested groups, and age-related change in vascular responsiveness to flicker light seems an unlikely risk factor for glaucoma.