Physics-informed deep generative learning for quantitative assessment of the retina.

Disruption of retinal vasculature is linked to various diseases, including diabetic retinopathy and macular degeneration, leading to vision loss. We present here a novel algorithmic approach that generates highly realistic digital models of human retinal blood vessels, based on established biophysical principles, including fully-connected arterial and venous trees with a single inlet and outlet. This approach, using physics-informed generative adversarial networks (PI-GAN), enables the segmentation and reconstruction of blood vessel networks with no human input and which out-performs human labelling. Segmentation of DRIVE and STARE retina photograph datasets provided near state-of-the-art vessel segmentation, with training on only a small (n = 100) simulated dataset. Our findings highlight the potential of PI-GAN for accurate retinal vasculature characterization, with implications for improving early disease detection, monitoring disease progression, and improving patient care.

The Role of Neuroglobin in Retinal Hemodynamics and Metabolism: A Real-Time Study.

Purpose: In this study, we used broadband near-infrared spectroscopy, a non-invasive optical technique, to investigate in real time the possible role of neuroglobin in retinal hemodynamics and metabolism. Methods: Retinae of 12 C57 mice (seven young and five old) and seven young neuroglobin knockouts (Ngb-KOs) were exposed to light from a low-power halogen source, and the back-reflected light was used to calculate changes in the concentration of oxygenated hemoglobin (HbO2), deoxygenated hemoglobin (HHb), and oxidized cytochrome c oxidase (oxCCO). Results: The degree of change in the near-infrared spectroscopy signals associated with HHb, HbO2, and oxCCO was significantly greater in young C57 mice compared to the old C57 mice (P < 0.05) and the Ngb-KO model (P < 0.005). Conclusions: Our results reveal a possible role of Ngb in regulating retinal function, as its absence in the retinae of a knockout mouse model led to suppressed signals that are associated with hemodynamics and oxidative metabolism. Translational Relevance: Near-infrared spectroscopy enabled the non-invasive detection of characteristic signals that differentiate between the retina of a neuroglobin knockout mouse model and that of a wild-type model. Further work is needed to evaluate the source of the signal differences and how these differences relate to the presence or absence of neuroglobin in the ganglion, bipolar, or amacrine cells of the retina.

Treatment of chronic diabetic macular oedema with intravitreal fluocinolone acetonide implant; real-life analysis of outcomes during overall treatment period.

PURPOSE: To assess the clinical efficacy of the fluocinolone acetonide (FA) intravitreal implant (Iluvien, Alimera Sciences) over a 12-month period in a population resistant to treatment with first-line anti-VEGF agents. METHODS: This study is a retrospective cohort study assessing functional and anatomical outcomes in 13 eyes of 12 patients treated for diabetic macular oedema (DMO) with a single fluocinolone implant (FA) (Iluvien) under real-world conditions. The follow-up period includes the time of first intravitreal treatment (incl anti-VEGF or short-lasting steroids) given until 12 months post FA implant insertion. Primary outcomes were best corrected visual acuity (BCVA), measured using the modified Early Treatment Diabetic Retinopathy Study (ETDRS) grading scale, and central foveal thickness (CFT), measured using Topcon 3DOCT-2000 (Topcon Inc) SD-OCT imaging. Mean BCVA and CFT were measured before anti-VEGF treatment, after anti-VEGF treatment, at the time of Iluvien implant insertion, and 6 and 12 months after Iluvien implant insertion. The t-paired sample test was used to ascertain statistical significance of changes in comparison of two samples while the ANOVA analysis was used in comparison of three or more samples. RESULTS: The baseline BCVA (SD) of the cohort prior to initiation of anti-VEGF treatment was 47.45 (12.27) ETDRS letters whilst the mean CFT (SD) was 579 (203) microns. Following completion of anti-VEGF therapy, the mean improvement in vision was 8.9 ETDRS letters (p = 0.1) whilst the mean reduction in CFT was 197 microns (p = 0.028). Mean BCVA (SD) at the time of insertion of the FA implant was 55.15 (11.16) ETDRS letters and mean (SD) CFT at time of insertion of the FA was 454.62 µm (109.51). Following the 12-month treatment period with the FA implant, BCVA (SD) was 62.15 (10.25) ETDRS letters (p = 0.0331) and the mean (SD) CFT was 404.36 µm (142.92), a change of -50.26 µm from baseline (p = 0.0369). CONCLUSIONS: This study has shown that statistically significant improvements in BCVA and CFT can be achieved over a 12-month period with the Iluvien implant. The implant has been shown to be a safe option in the treatment of DMO and may have a role to play in achieving good functional and anatomical outcomes in DMO while also reducing the frequency of follow-up appointments required to maintain stable vision in the working-age population.

Unilateral congenital non-syndromic retinal vessel dilation and tortuosity.

PURPOSE: To present a case of atypical unilateral developmental retinal vascular anomaly. OBSERVATIONS: A 10-year-old girl presented to her paediatrician after an absent red reflex was noted in a photograph. She had right anisometropic amblyopia and right iris heterochromia, but was otherwise healthy, with no visual complaints. Fundus examination revealed abnormal right retinal vasculature in keeping with an arteriovenous malformation (AVM). OCTA performed at age 16, showed large aberrant veins in the right eye, whereas OCTA B-Scans showed that the same eye had significantly higher retinal blood perfusion than the unaffected eye. CONCLUSIONS AND IMPORTANCE: OCTA is a valuable, non-invasive emerging method of evaluating patients with AVMs, with this patient having a unique unilateral presentation of a developmental anomaly, without evidence of progression or other vessel malformation. OCTA allowed assessment of flow between the affected and non-affected eye, quantifying the greater blood perfusion in the affected eye due to the AVM.

Widefield imaging with Clarus fundus camera vs slit lamp fundus examination in assessing patients referred from the National Health Service diabetic retinopathy screening programme.

OBJECTIVES: To compare diabetic retinopathy (DR) grading and management plan between virtual review using widefield Clarus imaging and macular optical coherence tomography (OCT) versus slit lamp clinical examination and macular OCT. METHOD: New referrals over 3 months from the National Diabetic Eye Screening programme (DESP) were screened. Patients who had both Clarus widefield imaging and macular OCT were included. All patients underwent slit lamp examination in clinic. Data obtained from electronic patient records included referral reason, DR grading and management plan. Two graders retrospectively reviewed imaging and formulated a management plan blinded to results from patients' clinic visit. Results from virtual examination were compared with those from slit lamp examination. RESULTS: One-hundred and two eyes of 51 patients were assessed. 11 fundus photos from 7 patients and 15 fundus photos from 10 patients were deemed inadequate by grader G1 and G2, respectively. Eighteen (35%) patients and 11 (22%) patients from virtual assessment by G1 and G2, respectively were found to need a face a face appointment to aid diagnosis. Compared to slit lamp examination, 15% and 7.5% of patients from G1 and G2's virtual assessment respectively had different proposed management plan. Agreement of DR grading between both virtual graders and slit lamp examination was fair (Kappa's coefficient = 0.56). One case of slit lamp noted retinal neovascularization, which was graded as background retinopathy by DESP was also graded as such on virtual assessment. CONCLUSION: Widefield Clarus and OCT imaging allowed two-thirds of DESP referrals to be safely managed virtually.

Four-year outcomes of aflibercept treatment for neovascular age-related macular degeneration: Results from real-life setting.

BACKGROUND: To assess long-term structural and functional outcomes of intravitreal aflibercept (Eylea®) treatment for neovascular macular degeneration (nAMD) in a real-word setting. DESIGN AND METHODS: This was a retrospective, single-centre, non-randomized interventional cohort analysis. Data from treatment-naive patients with nAMD funded for treatment with intravitreal aflibercept in the period between 1 September 2013 and 28 February 2014 and who finished 4-year follow-up entered the analysis. Epidemiological data, visual acuity (VA) measured on ETDRS charts and injection numbers were recorded. Spectral domain optical coherence tomography (SD-OCT) data including presence or absence of macular fluid and automated central subfield macular thickness (CSMT) at year 1, 2, 3 and 4 were also recorded. RESULTS: Ninety-four eyes of 89 patients finished 4-year follow-up. The mean number of aflibercept injections received over 4 years was 19.3. At baseline, the mean VA (SD) (Snellen) was 54.1 ± 15.5 (20/100) ETDRS letters whilst the mean CSM (SD) was 296 ± 81 µm. At 4 years, the mean VA (SD) (Snellen) was 60.4 ± 20.0 (20/63) ETDRS letters (p < 0.0001). Mean CSMT (SD) was 218 ± 79 µm (p < 0.0001). Thirty-three percent of eyes gained ⩾15 ETDRS letters at end of 4 years, and 66 (70%) eyes had no macular fluid at the end of the follow-up. CONCLUSION AND RELEVANCE: The results suggest that good long-term morphological and functional treatment outcomes can be achieved using intravitreal aflibercept for nAMD in a real-life clinical setting.

One-year real-life results on effect of intravitreal aflibercept in patients with diabetic macular oedema switched from ranibizumab.

PURPOSE: To assess visual and optical coherence tomography-derived anatomical outcomes of treatment with intravitreal aflibercept (Eylea®) for diabetic macular oedema in patients switched from intravitreal ranibizumab (Lucentis®). DESIGN: Retrospective, cohort study. PARTICIPANTS: Ninety eyes (of 67 patients) receiving intravitreal anti-vascular endothelial growth factor therapy were included. METHODS: This is a retrospective, real-life, cohort study. Each patient had visual acuity measurements and optical coherence tomography scans performed at baseline and 12 months after the first injection of aflibercept was given. MAIN OUTCOME MEASURES: We measured visual acuities in Early Treatment Diabetic Retinopathy Study letters, central foveal thickness and macular volume at baseline and at 12 months after the first aflibercept injection was given. RESULTS: Ninety switched eyes were included in this study. The mean (standard deviation) visual acuity was 63 (15.78) Early Treatment Diabetic Retinopathy Study letters. At baseline, the mean (standard deviation) central foveal thickness was 417.7 (158.4) µm and the mean macular volume was 9.96 (2.44) mm3. Mean change in visual acuity was +4 Early Treatment Diabetic Retinopathy Study letters (p = 0.0053). The mean change in macular volume was -1.53 mm3 in SW group (p = 0.21), while the change in central foveal thickness was -136.8 µm (p = 0.69). CONCLUSION: There was a significant improvement in visual acuity and in anatomical outcomes in the switched group at 12 months after commencing treatment with aflibercept for diabetic macular oedema.

Intravitreal aflibercept for diabetic macular oedema in real-world: 36-month visual acuity and anatomical outcomes.

BACKGROUND/AIMS: To assess structural and functional outcomes of treatment with intravitreal aflibercept (®Eylea) for diabetic macular oedema in treatment-naïve patients. METHODS: Sixty-four eyes receiving intravitreal anti-vascular endothelial growth factor therapy were included in the data analysis of this retrospective, real-life study which follow-up was 3 years. Each patient had corrected visual acuity in Early Treatment Diabetic Retinopathy Study letters and optical coherence tomography central foveal thickness and macular volume performed at baseline, 12, 24 and 36 months. Patients were initiated on a loading phase of five 1-monthly intravitreal aflibercept injections, followed by injections if needed as per clinicians' discretion. RESULTS: The mean number of aflibercept injections received over 3 years was 12.59. At baseline, the mean visual acuity (standard deviation) (Snellen) was 61.45 (16.30) (20/63) Early Treatment Diabetic Retinopathy Study letters, the mean central foveal thickness (standard deviation) was 422 (138) µm, while the mean macular volume (standard deviation) was 9.51 (2.01) mm3. At 36 months, the mean visual acuity (standard deviation) (Snellen) was 68.34 (13.66) (20/50) Early Treatment Diabetic Retinopathy Study letters (p = .0003). Mean central foveal thickness (standard deviation) was 303 (106) µm (p < .0001) and mean macular volume (standard deviation) was 8.35 (1.62) mm3 (p = .0022) at 36 months. Sixteen (25%) eyes gained ≥15 ETDRS letters at month 36, and 33 (52%) eyes had a decrease in central foveal thickness of ≥ 100 µm at the same time. CONCLUSION: There was a significant improvement in visual acuity and in anatomical outcomes in aflibercept-treated eyes at 36 months after commencing treatment for diabetic macular oedema in real-life settings. The good vision and anatomical outcomes were maintained over second and third year of treatment with mean 2.93 and 2.57 intravitreal injections, respectively.

Widefield optical coherence tomography angiography for early detection and objective evaluation of proliferative diabetic retinopathy.

PURPOSE: To evaluate the utility of widefield optical coherence tomography angiography (WF-OCTA) compared with clinical examination in grading diabetic retinopathy in patients diagnosed clinically with proliferative diabetic retinopathy (PDR) or severe non-proliferative diabetic retinopathy (NPDR). DESIGN: This retrospective observational case series included patients diagnosed clinically with PDR or severe NPDR. Patients underwent standard clinical examination and WF-OCTA imaging (PLEX Elite 9000, Carl Zeiss Meditec AG) using 12×12 montage scans between August 2018 and January 2019. Two trained graders identified neovascularisation at the disc (NVD) and neovascularisation elsewhere (NVE) on WF-OCTA which were compared with the clinical examination, and to ultra-widefield fluorescein angiography (UWFA) when available. RESULTS: Seventy-nine eyes of 46 patients were evaluated. Of those, 57 eyes were diagnosed clinically with PDR, and 22 with severe NPDR. NVD was detected on OCTA-B scan as preretinal hyperreflective material (PRHM) in 39 eyes (100%) with evident flow signals in 79.5% compared with 51.3% detected clinically. We further classified NVD on OCTA into four subtypes and found that subtypes 1 and 2 could not be seen on clinical examination alone. WF-OCTA detected NVE in 81% of the cases compared with 55.7% detected clinically. Using WF-OCTA resulted in a higher percentage of PDR grading (88.6%) than on clinical examination (72.2%). When available, UWFA confirmed the WF-OCTA diagnosis in the majority of cases. CONCLUSION: This study demonstrates that WF-OCTA has a higher detection rate of PDR than clinical examination. This suggests that this modality could be used non-invasively for the purpose of early detection and characterisation of neovascularisation.

An open-source data set of anti-VEGF therapy in diabetic macular oedema patients over 4 years and their visual acuity outcomes.

OBJECTIVES: The objective of this paper is to evaluate visual acuity (VA) outcomes of intravitreal anti-vascular endothelial growth factor (VEGF) in diabetic macular oedema (DMO). METHODS: In this retrospective cohort study, electronic medical records for all patients undergoing intravitreal injections in a tertiary referral centre between March 2013 and October 2018 were analysed. Treatment response in terms of VA outcomes was reported for all eyes over a 4-year observation period. RESULTS: Our cohort includes 2614 DMO eyes of 1964 patients over 48 months. Cox proportional-hazards modelling identified injection number (hazard ratio (HR) = 1.18), male gender (HR = 1.13) and baseline VA (HR = 1.09) as independent predictors to reach a favourable visual outcome of more than 70 Early Treatment Diabetic Retinopathy Study letters. Half of our cohort reached 70 letters 1.9 months after starting anti-VEGF therapy. Of those that reached 70 letters, 50% fell below 70 letters by 14.7 months. CONCLUSION: To date, this is the largest single centre cohort study and over the longest observation period reporting on real-life outcomes of anti-VEGF in DMO. We have made an anonymised version of our data set available on an open-source data repository as a resource for clinical researchers globally.

Phenotyping of retinal neovascularization in ischemic retinal vein occlusion using wide field OCT angiography.

BACKGROUND/OBJECTIVES: Abnormal retinal neovascularization caused by ischemic retinal vein occlusion (RVO) is a frequent cause of visually significant vitreous hemorrhage. The early detection of new vessels may be challenging and often requires the use of invasive tests such as fundus fluorescein angiography (FA). We demonstrate the use of wide-field optical coherence tomography angiography (WF-OCTA) in the detection and characterization of neovascularization secondary to ischemic RVO. SUBJECTS/METHODS: We conducted a retrospective observational case series of patients diagnosed with ischemic RVO between August 2018 and March 2019, who underwent WF-SS-OCTA imaging (PLEX Elite 9000, Carl Zeiss Meditec). We performed real-life montage imaging, covering the involved area and compared the findings of WF-SS-OCTA to standard clinical examination and when available, ultrawide-field fluorescein angiography (UWF-FA, Optos 200TX). RESULTS: In the included 39 eyes with ischemic RVO, neovascularization elsewhere (NVE) was encountered in 16 of 39 eyes (41%) on WF-OCTA and were characterized as sea-fan type vessels and nodular type vessels, based on their appearance and localization. NVE was identified in 4/39 eyes on standard clinical examination, equating to a detection rate of 10.3%. All were of a sea-fan morphology. In one case, NVE found on WF-OCTA was not observed on UWF-FA, which was a nodular type. Neovascularization of the disc (NVD) was detected in one eye. CONCLUSIONS: WF-OCTA may become a useful noninvasive tool in the detection of neovascularization in patients with ischemic RVO. Furthermore, the characterization of different morphologies of neovascularization detected by WF-OCTA could be of clinical relevance.

A prospective randomized trial of intravitreal bevacizumab or laser therapy in the management of diabetic macular edema (BOLT study) 12-month data: report 2.

PURPOSE: To report the findings at 1 year of a study comparing repeated intravitreal bevacizumab (ivB) and modified Early Treatment of Diabetic Retinopathy Study (ETDRS) macular laser therapy (MLT) in patients with persistent clinically significant diabetic macular edema (CSME). DESIGN: Prospective, randomized, masked, single-center, 2-year, 2-arm clinical trial. PARTICIPANTS: A total of 80 eyes of 80 patients with center-involving CSME and at least 1 prior MLT. METHODS: Subjects were randomized to either ivB (6 weekly; minimum of 3 injections and maximum of 9 injections in the first 12 months) or MLT (4 monthly; minimum of 1 treatment and maximum of 4 treatments in the first 12 months). MAIN OUTCOME MEASURES: The primary end point was the difference in ETDRS best-corrected visual acuity (BCVA) at 12 months between the bevacizumab and laser arms. RESULTS: The baseline mean ETDRS BCVA was 55.7+/-9.7 (range 34-69) in the bevacizumab group and 54.6+/-8.6 (range 36-68) in the laser arm. The mean ETDRS BCVA at 12 months was 61.3+/-10.4 (range 34-79) in the bevacizumab group and 50.0+/-16.6 (range 8-76) in the laser arm (P = 0.0006). Furthermore, the bevacizumab group gained a median of 8 ETDRS letters, whereas the laser group lost a median of 0.5 ETDRS letters (P = 0.0002). The odds of gaining > or =10 ETDRS letters over 12 months were 5.1 times greater in the bevacizumab group than in the laser group (adjusted odds ratio, 5.1; 95% confidence interval, 1.3-19.7; P = 0.019). At 12 months, central macular thickness decreased from 507+/-145 microm (range 281-900 microm) at baseline to 378+/-134 microm (range 167-699 microm) (P<0.001) in the ivB group, whereas it decreased to a lesser extent in the laser group, from 481+/-121 microm (range 279-844 microm) to 413+/-135 microm (range 170-708 microm) (P = 0.02). The median number of injections was 9 (interquartile range [IQR] 8-9) in the ivB group, and the median number of laser treatments was 3 (IQR 2-4) in the MLT group. CONCLUSIONS: The study provides evidence to support the use of bevacizumab in patients with center-involving CSME without advanced macular ischemia.

Longitudinal follow-up of dome-shaped macula.

BACKGROUND/OBJECTIVES: To determine if the presence of sub-retinal fluid (SRF) was associated with reduced vision in dome-shaped macula (DSM), and to assess its effect and response to treatment during follow-up. METHODS: Patients were identified retrospectively. Baseline and follow-up data were recorded. The diagnosis of DSM, and presence or absence of SRF and intra-retinal fluid (IRF) was confirmed using Spectral Domain-Optical Coherence Tomography (SD-OCT). Decisions to treat oedema were based on clinician preference. RESULTS: 193 eyes of 106 patients (71 female) were confirmed to have DSM. Overall mean duration of follow-up for this cohort was 3.5 years. Mean BRVA for all eyes at baseline was 0.38 (range: -0.20 to 'light perception'). A significant difference was noted in mean baseline BRVA between those eyes with SRF compared with those without SRF at baseline (0.48 vs. 0.31, p < 0.001). Intra-retinal fluid moderately correlated with poorer baseline BRVA (r = 0.31, p < 0.003). No significant change in BRVA was noted during follow-up. No significant effect of treatment on BRVA was observed. CONCLUSIONS: The presence of SRF at baseline was associated with poorer vision. Vision appears to remain stable irrespective of the presence or absence of SRF at baseline. The treatments administered in this cohort did not affect final vision or SRF.

Intravitreal aflibercept for diabetic macular oedema: Moorfields' real-world 12-month visual acuity and anatomical outcomes.

OBJECTIVES: To assess structural and functional outcomes of treatment with intravitreal aflibercept (Eylea®) for diabetic macular oedema in treatment-naive patients. DESIGN: This is a retrospective, real-life, cohort study. PARTICIPANTS AND METHODS: In all, 92 diabetic patients (102 eyes) receiving intravitreal anti-vascular endothelial growth factor therapy were included. A total of 99 aflibercept-treated eyes were included in the statistical analysis. Each patient had corrected visual acuity in Early Treatment Diabetic Retinopathy Study letters and optical coherence tomography central foveal thickness and macular volume performed at baseline and 12 months. Patients were initiated on a loading phase of five monthly intravitreal aflibercept injections, followed by injections if needed as per clinicians' discretion. RESULTS: The mean number of aflibercept injections received was 6.92. At baseline, the mean visual acuity (standard deviation; Snellen) was 59.7 (16.1) (20/63) Early Treatment Diabetic Retinopathy Study letters, the mean central foveal thickness (standard deviation) was 431 (129) µm, while the mean macular volume (standard deviation) was 9.53 (1.79) mm3. At 12 months, the mean visual acuity (standard deviation; Snellen) was 69.6 (15.2; 20/40) Early Treatment Diabetic Retinopathy Study letters (p < .0001). Mean central foveal thickness (standard deviation) was 306 (122) µm (p < .0001) and mean macular volume (standard deviation) was 8.43 (1.58) mm3 (p < .0001) at 12 months; 33 (33.67%) eyes gained ⩾15 Early Treatment Diabetic Retinopathy Study letters at month 12, and 50 (55.55%) eyes had a decrease in central foveal thickness of ⩾100 µm. CONCLUSION: There was a significant improvement in visual acuity and in anatomical outcomes in aflibercept-treated eyes at 12 months after commencing treatment for diabetic macular oedema in real-life settings.

Preservation of the Foveal Avascular Zone in Achromatopsia Despite the Absence of a Fully Formed Pit.

Purpose: To examine the foveal avascular zone (FAZ) in patients with congenital achromatopsia (ACHM). Methods: Forty-two patients with genetically confirmed ACHM were imaged either with Optovue's AngioVue system or Zeiss's Plex Elite 9000, and the presence or absence of a FAZ was determined. For images where a FAZ was present and could be confidently segmented, FAZ area, circularity index, and roundness were measured and compared with previously published normative values. Structural optical coherence tomography images were acquired to assess the degree of foveal hypoplasia (number and thickness of inner retinal layers present at the fovea). Results: A FAZ was present in 31 of 42 patients imaged (74%), although no determination could be made for 11 patients due to poor image quality (26%). The mean ± SD FAZ area for the ACHM retina was 0.281 ± 0.112 mm2, which was not significantly different from the previously published normative values (P = 0.94). However, their FAZs had decreased circularity (P < 0.0001) and decreased roundness (P < 0.0001) compared to the normative cohort. In the patients with ACHM examined here, the FAZ area decreased as the number and thickness of the retained inner retinal layers increased. Conclusions: Our data demonstrate that despite the presence of foveal hypoplasia, patients with ACHM can have a FAZ. This is distinct from other conditions associated with foveal hypoplasia, which generally show an absence of the FAZ. In ACHM, FAZ formation does not appear to be sufficient for complete pit formation, contrary to some models of foveal development.

Three-Year Outcomes of Aflibercept Treatment for Neovascular Age-Related Macular Degeneration: Evidence from a Clinical Setting.

INTRODUCTION: To report 3-year treatment outcomes with intravitreal aflibercept injections for neovascular age-related macular degeneration (nAMD) in routine clinical practice. METHODS: This was a retrospective, single-centre, non-randomized interventional case series analysis. Data from treatment-naïve patients with nAMD treated between 1 October 2013 and 31 February 2014 were included in the analysis. Data including age, gender, vision acuity (VA) measured on Early Treatment of Diabetic Retinopathy Study charts (ETDRS) and injection numbers were recorded. Spectral domain optical coherence tomography (SD-OCT) data including presence or absence of macular fluid and automated central subfield macular thickness (CSMT) at year 1, 2 and 3 were also recorded. RESULTS: Of the 157 eyes of 148 patients treated, data from 108 eyes of 102 patients were available at 3-year follow-up. The mean (± SD) age was 80.6 ± 8.3 years with a mean of 154.5 ± 5.4 weeks follow-up. The mean VA changed from 54.4 ± 16 letters at baseline to 60.3 ± 18.1 letters (VA gain 5.9 ± 13.8 letter gain) at 1 year, to 60.8 ± 17.4 letters (VA gain 6.4 ± 14.9 letters) at 2 years and to 61.0 ± 16.6 letters (VA gain 6.6 ± 15.4 letters) at 3 years. The reduction in CSMT was 77.9 ± 101.4 µm with absence of macular fluid in 71% of eyes. The total mean number of injections was 15.9 ± 6.1 at year 3. CONCLUSION: The results suggest that good long-term morphological and functional treatment outcomes can be achieved using aflibercept for nAMD in a clinical setting.

Implementation of medical retina virtual clinics in a tertiary eye care referral centre.

BACKGROUND: The increasing incidence of medical retinal diseases has created capacity issues across UK. In this study, we describe the implementation and outcomes of virtual medical retina clinics (VMRCs) at Moorfields Eye Hospital, South Division, London. It represents a promising solution to ensure that patients are seen and treated in a timely fashion METHODS: First attendances in the VMRC (September 2016-May 2017) were included. It was open to non-urgent external referrals and to existing patients in a face-to-face clinic (F2FC). All patients received visual acuity testing, dilated fundus photography and optical coherence tomography scans. Grading was performed by consultants, fellows and allied healthcare professionals. Outcomes of these virtual consultations and reasons for F2FC referrals were assessed. RESULTS: A total number of 1729 patients were included (1543 were internal and 186 external referrals). The majority were diagnosed with diabetic retinopathy (75.1% of internal and 46.8% of external referrals). Of the internal referrals, 14.6% were discharged, 54.5% continued in VMRC and 30.9% were brought to a F2FC. Of the external referrals, 45.5% were discharged, 37.1% continued in VMRC and 17.4% were brought to a F2FC. The main reason for F2FC referrals was image quality (34.7%), followed by detection of potentially treatable disease (20.2%). CONCLUSION: VMRC can be implemented successfully using existing resources within a hospital eye service. It may also serve as a first-line rapid-access clinic for low-risk referrals. This would enable medical retinal services to cope with increasing demand and efficiently allocate resources to those who require treatment.

Effect of glycosylated hemoglobin on response to ranibizumab therapy in diabetic macular edema: real-world outcomes in 312 patients.

OBJECTIVE: To investigate the effect of serum glycosylated hemoglobin (HbA1c) on the outcomes of ranibizumab therapy for diabetic macular edema (DME). DESIGN: Retrospective cohort study. PARTICIPANTS: Patients receiving ranibizumab injections for centre-involving DME in a National Health Service setting. METHODS: The Moorfields OpenEyes database was used to study eyes with DME treated with ranibizumab from October 2013 to November 2015 at the Moorfields City Road, Ealing, Northwick Park, and St George's Hospital sites. Only eyes receiving a minimum of 3 injections and completing 12 months of follow-up were included. If both eyes received treatment, the first eye treated was analyzed. When both eyes received initial treatment simultaneously, random number tables were used to select the eye for analysis. HbA1c was tested at the initiation of ranibizumab treatment. Multivariate regression analysis was used to identify relationships between HbA1c and the outcome measures. OUTCOMES: The primary outcome was change in visual acuity (VA) Early Treatment of Diabetic Retinopathy study (ETDRS) letters. The secondary outcomes were change in central subfield thickness (CSFT) and macular volume (MV), as well as number of injections in year 1. RESULTS: Three hundred and twelve eyes of 312 patients were included in the analysis. HbA1c was not related to change in VA (p = 0.577), change in CSFT (p = 0.099), change in MV (p = 0.082), or number of injections in year 1 (p = 0.859). CONCLUSIONS: HbA1c is not related to functional or anatomical outcomes at 1 year in DME treated with ranibizumab.

Photoreceptor mitochondrial oxidative stress in early experimental autoimmune uveoretinitis.

AIMS: In early S-antigen induced experimental uveitis (EAU), photoreceptor mitochondrial proteins are nitrated prior to macrophage infiltration of the retina, suggesting that oxidative stress is an initial event in the development of EAU. We attempted to detect the oxidative stress and localise it in the EAU retina. METHODS: Lewis rats were immunised with S-antigen in complete Freund's adjuvant (CFA). Animals were injected with CFA alone and non-immunised animals served as controls. Immunised and non-immunised animals were killed on day 5 and subsequent days. Isolated retinas were processed for inducible nitric oxide synthase (iNOS), tumour necrosis factor (TNF)alpha, interferon (IFN)gamma, interleukin (IL)Ialpha and CD28 expression by real time polymerase chain reaction. In addition, iNOS was colocalised with cytochrome c oxidase on day 5 of EAU. Oxidative stress was detected by 2', 7'-dichlorodihydrofluorescein diacetate and localised by a mitochondrial specific marker. Leucocyte and T cell infiltration in the retina/choroid was evaluated by immunohistochemistry. RESULTS: The iNOS, TNFalpha, IFNgamma, IL1alpha and CD28 transcripts were significantly upregulated on day 5 in EAU, and iNOS was colocalised with cytochrome c oxidase in the photoreceptor mitochondria. Oxidative stress was seen primarily in the photoreceptor mitochondria. Occasional T cells were present in the retina at this stage. CONCLUSIONS: During early EAU, mitochondrial oxidative stress is selectively noted in the photoreceptor inner segments. The oxidative stress appears to result from iNOS upregulation in the photoreceptor mitochondria and cytokine generation in the retina by a few antigen specific infiltrating T cells.

Neuroglobin in normal retina and retina from eyes with advanced glaucoma.

BACKGROUND: Neuroglobin is a neurone specific respiratory protein that reversibly binds oxygen. Neuroglobin was discovered in 2000, initially in brain and later, at a 100 times greater concentration, in mouse retina. This protein may be involved in oxygen transport, and/or protection against oxidative stress or premature apoptosis. AIM: To examine the expression of neuroglobin in normal human retina and also in retina from eyes with advanced glaucoma, where hypoxia and ischaemia may be pathological factors. METHODS: Immunofluorescence and electron microscopy were used to examine sections of normal human retina and retina from eyes with end-stage glaucoma. RESULTS: Staining for neuroglobin was present in the plexiform layers and the photoreceptor inner segments in human retina, and increased expression was found to occur in these areas, as well as in the nuclear layers in advanced glaucoma. Much less staining for neuroglobin was present in the other retinal layers. CONCLUSION: Neuroglobin is found in those layers of the human retina that are rich in mitochondria and/or synapses, and consume the highest amount of oxygen. Neuroglobin may be involved in oxygen supply to mitochondria, or in protection from oxidative stress or apoptosis. Neuroglobin expression is increased in advanced glaucoma, and it may protect against hypoxic, ischaemic or oxidative stress, which are thought to be pathological factors that affect the retina in glaucoma.