The Natural History of Retinal Sensitivity Loss in Diabetic Macular Ischemia over One Year Evaluated by Microperimetry.

Background/Objectives: This one-year prospective observational study, conducted at two centers, aimed to report the natural history of retinal sensitivity (RS) loss in diabetic macular ischemia (DMI). Methods: Patients with stable-treated proliferative diabetic retinopathy (PDR) were recruited if there was evidence of DMI on optical coherence tomography angiography, defined as a foveal avascular zone ≥ 0.5 mm2 or parafoveal capillary dropout ≥ 1 quadrant. The minimal visual acuity required for performing microperimetry (MP) was ≥54 Early Treatment Diabetic Retinopathy Study letters (Snellen equivalent 20/80). The overall RS (oRS) and pointwise sensitivity (PWS) within the 3 × 3 mm macula were assessed at baseline and twelve months. A value <25 decibels (dB) was defined as impaired RS, and a decrease of 2 and 7 dB was regarded as mild and severe loss, respectively. Results: A total of 88 patients (97 eyes) were included. No statistically significant MP changes were detected at one year. However, 10% of the cohort lost oRS ≥ 2 dB, and 73% lost ≥2 dB PWS in ≥5 loci, whereas 1% lost oRS ≥ 7 dB, and 4% lost ≥7 dB PWS in ≥5 loci. The foveola and temporal parafovea were the most vulnerable to severe RS loss. Compared to their counterpart, eyes with baseline oRS ≥ 25 dB had significantly more RS loss in the macula and superior parafovea (55% versus 32% and 53% versus 28%, both p = 0.01). Conclusions: Rather than oRS loss, ≥2 dB loss in PWS in ≥5 loci is a more feasible outcome measure for clinical trials in DMI.

Optical Coherence Tomography Angiography as a Diagnostic Tool for Diabetic Retinopathy.

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes mellitus, leading to visual impairment if left untreated. This review discusses the use of optical coherence tomography angiography (OCTA) as a diagnostic tool for the early detection and management of DR. OCTA is a fast, non-invasive, non-contact test that enables the detailed visualisation of the macular microvasculature in different plexuses. OCTA offers several advantages over fundus fluorescein angiography (FFA), notably offering quantitative data. OCTA is not without limitations, including the requirement for careful interpretation of artefacts and the limited region of interest that can be captured currently. We explore how OCTA has been instrumental in detecting early microvascular changes that precede clinical signs of DR. We also discuss the application of OCTA in the diagnosis and management of various stages of DR, including non-proliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR), diabetic macular oedema (DMO), diabetic macular ischaemia (DMI), and pre-diabetes. Finally, we discuss the future role of OCTA and how it may be used to enhance the clinical outcomes of DR.

Topographic Correlation of Microperimetry With Structural Characteristics in Diabetic Macular Ischemia.

PURPOSE: This study aimed to determine the threshold for defining abnormal retinal sensitivity (RS) that correlates with structural changes in diabetic macular ischemia (DMI) patients with stable treated proliferative diabetic retinopathy (PDR). DESIGN: Prospective cross-sectional study. METHODS: In a single center, we recruited 85 eyes (67 patients) with stable treated PDR with best-corrected visual acuity (BCVA) ≥54 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (Snellen equivalent 20/80) and optical coherence tomography angiography evidence of DMI. The function-function and function-structure correlation were assessed. Two preselected thresholds in overall RS (oRS), 25 decibels (dB) and age-matched normative data (AMND), were tested on their ability to reflect abnormal anatomy in DMI. Finally, a multivariable regression model was established to depict the relationship between the oRS and various parameters. RESULTS: The oRS showed only a modest correlation with BCVA and low-luminance visual acuity (LLVA). The whole-image deep vessel density (wiDVD) was the most reliable vascular metric correlated with RS. For every 1% decline in the wiDVD, the oRS decreased by 0.37 dB (P < .001) after multivariable adjustment. Furthermore, both a reduction of oRS to <25 dB or below AMND could differentiate eyes with FAZ ≥0.5 mm2, whole image superficial vessel density (wiSVD) <37.7%, wiDVD <41.9%, and the presence of disorganization of the retinal inner layers (DRIL) from their counterparts. CONCLUSIONS: The absolute value of 25 dB in oRS is worth considering as a trial endpoint, because it does not require complex calculation and closely reflects the structural abnormalities in DMI.

Study protocol on prevalence of non-exudative macular neovascularisation and its contribution to prediction of exudation in fellow eyes with unilateral exudative AMD (EYE-NEON).

PURPOSE: Fellow eyes of patients with unilateral neovascular age-related macular degeneration (nAMD) are at risk of developing macular neovascularisation (MNV). These eyes may first develop subclinical non-exudative MNV (neMNV) before they leak to form exudative MNV (eMNV). The EYE NEON study is a 2-year study aimed at estimating the prevalence and incidence of neMNV and evaluating its role as a predictor for conversion to neovascular AMD. METHODS: EYE NEON is a multicentre study that will run in retinal clinics across 25 National Health Service with the aim to recruit 800 patients with new onset nAMD in the first eye. The fellow-eye with no evidence of nAMD at baseline will be the study eye. All study eyes will have OCT and OCTA done at first and second year following first anti-VEGF treatment to the first eye (non-study eye), with new onset nAMD. We will estimate the prevalence and incidence of neMNV over 2 years, rate of conversion from neMNV to eMNV and numbers initiated on treatment for neovascular AMD in the study eye will be reported. Predictive models of conversion including neMNV with other demographic and imaging parameters will be developed. CONCLUSION: The study design with proposed target sample size is sufficient to evaluate the retinal imaging characteristics of the study eyes with and without neMNV and develop predictive models to inform risk of conversion to nAMD.

Characterization of the Structural and Functional Alteration in Eyes with Diabetic Macular Ischemia.

OBJECTIVE: To investigate the relative effect of disorganization of the retinal inner layers (DRIL) and ellipsoid zone (EZ) loss on visual function in diabetic macular ischemia (DMI). DESIGN: Prospective cross-sectional observational study. PARTICIPANTS: Patients with stable treated proliferative diabetic retinopathy (PDR) without center-involved diabetic macular edema were recruited at the Moorfields Eye Hospital from December 2019 to November 2021. The main inclusion criteria were best-corrected visual acuity (BCVA) of ≥ 40 ETDRS letters (Snellen equivalent 20/160) with OCT angiography (OCTA) evidence of DMI in ≥ 1 eye. METHODS: Each eligible eye of the recruited patients was assessed for BCVA, OCT, and OCTA metrics. The prespecified OCT parameters were DRIL and subfoveal EZ loss. Generalized estimating equations were used. MAIN OUTCOMES MEASURES: The frequency of DRIL and EZ loss, their relative contributions to vision loss, and their associations with microvascular alterations were evaluated. RESULTS: A total of 125 eyes of 86 patients with PDR were enrolled; 104 (83%) eyes had a BCVA of ≥ 70 letters. Disorganization of the retinal inner layers was more prevalent than EZ loss (46% [58 eyes] vs. 19% [24 eyes]). On average, the presence of DRIL had a more pronounced impact on vision, retinal thickness, and microvascular parameters than EZ loss. After multivariable adjustment, the odds of coexisting DRIL increased by 12% with every letter decrease in BCVA; however, there was no statistically significant association of subfoveal EZ loss with BCVA. In eyes with DRIL in the absence of EZ loss, the BCVA declined significantly by 6.67 letters compared with eyes with no DRIL nor EZ loss (95% confidence interval [CI], -9.92 to -3.41; P < 0.001). However, if DRIL and EZ loss coexisted, the resultant BCVA was 13.22 letters less than eyes without these structural abnormalities (95% CI, -18.85 to -7.59; P < 0.001). CONCLUSIONS: In patients with DMI with a Snellen visual acuity of 20/160 or better, eyes with DRIL were associated with more visual function loss and retinal blood circulation alterations than those with subfoveal EZ loss only.

Correlation of Optical Coherence Tomography Angiography Characteristics with Visual Function to Define Vision-Threatening Diabetic Macular Ischemia.

The thresholds of macular microvasculature parameters associated with mild visual impairment in diabetic macular ischemia (DMI) patients are unclear. Therefore, this prospective observational study is aimed at demonstrating the optical coherence tomography angiography parameters that best correlate with mild visual impairment (<70 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, Snellen equivalent 20/40) in DMI. The study was completed at the Moorfields Eye Hospital from December 2019 to August 2021. A total of 123 eyes of 87 patients with stable-treated proliferative diabetic retinopathy following panretinal photocoagulation were recruited. DMI was defined as an irregular foveal avascular zone (FAZ) area ≥ 0.5 mm2 or a smaller FAZ area with parafoveal capillary dropout in at least one quadrant. The analysis showed that the whole image deep vascular complex vessel density (DVC VD) in the 3 × 3 mm area had the best discriminatory ability to identify participants with mild visual impairment at 41.9% (area under the curve = 0.77, sensitivity 94%, specificity 54%, likelihood ratio [LR] = 2.04), and the FAZ area had the greatest post-test LR = 4.21 at 0.64 mm2. The 3 × 3 mm whole image DVC VD and FAZ area cutoffs are useful for screening vision-threatening DMI, but DVC VD has low specificity.

Diabetic macular ischaemia- a new therapeutic target?

Diabetic macular ischaemia (DMI) is traditionally defined and graded based on the angiographic evidence of an enlarged and irregular foveal avascular zone. However, these anatomical changes are not surrogate markers for visual impairment. We postulate that there are vascular phenotypes of DMI based on the relative perfusion deficits of various retinal capillary plexuses and choriocapillaris. This review highlights several mechanistic pathways, including the role of hypoxia and the complex relation between neurons, glia, and microvasculature. The current animal models are reviewed, with shortcomings noted. Therefore, utilising the advancing technology of optical coherence tomography angiography (OCTA) to identify the reversible DMI phenotypes may be the key to successful therapeutic interventions for DMI. However, there is a need to standardise the nomenclature of OCTA perfusion status. Visual acuity is not an ideal endpoint for DMI clinical trials. New trial endpoints that represent disease progression need to be developed before irreversible vision loss in patients with DMI. Natural history studies are required to determine the course of each vascular and neuronal parameter to define the DMI phenotypes. These DMI phenotypes may also partly explain the development and recurrence of diabetic macular oedema. It is also currently unclear where and how DMI fits into the diabetic retinopathy severity scales, further highlighting the need to better define the progression of diabetic retinopathy and DMI based on both multimodal imaging and visual function. Finally, we discuss a complete set of proposed therapeutic pathways for DMI, including cell-based therapies that may provide restorative potential.

A comparative study of orthokeratology and low-dose atropine for the treatment of anisomyopia in children.

Myopic anisometropia (anisomyopia) is a specific type of refractive error that may cause fusion impairment, asthenopia, and aniseikonia. It is sometimes severe enough to reduce the quality of life. Several studies have investigated the treatment effects of orthokeratology (Ortho-K) and topical atropine on anisomyopia control. However, no study has compared these two interventions simultaneously until now. The cohort of this retrospective study included 124 children with anisomyopia who were treated with binocular Ortho-K lenses, 0.01% atropine, or 0.05% atropine. After a 2-year follow-up, the inter-eye difference in axial length (AL) significantly decreased in the Ortho-K group (P = 0.015) and remained stable in the two atropine groups. When comparing the myopia control effect, the use of Ortho-K lenses resulted in an obviously smaller change in AL than the use of 0.01% and 0.05% atropine (P < 0.01). Ortho-K treatment may reduce the degree of anisomyopia and stabilise the progression of myopia. Hence, Ortho-K might be a better choice for anisomyopic children.

Sequential changes to intraocular lens dislocation caused by vigorous ocular massage: A case report.

RATIONALE: Although intraocular lens (IOL) dislocations have been reported after uneventful cataract surgeries, no sequential changes have ever been demonstrated. Our case showed the sequential changes to IOL dislocation caused by vigorous ocular massage. PATIENT CONCERNS: A 42-year-old man complained of blurred vision in the left eye 8 years after uneventful phacoemulsification. The IOL was still well-centered, but curvilinear tears of the anterior and posterior capsule along the optic border of IOL and vitreous herniation were noted. In the following month, the IOL subluxated inferiorly. A careful history taking revealed a recent habit of vigorous ocular massage. The subluxation was stable for 2 years after avoiding ocular massage, but dislocation into vitreous occurred after taking a spring water bath (spa) bath with massage. DIAGNOSIS: IOL dislocation. INTERVENTIONS: Pars plana vitrectomy to remove the dislocated IOL and implantation of a 3-piece IOL into sulcus were performed. OUTCOMES: The IOL was well-centered. The visual acuity returned to 20/20. LESSONS: Ocular massage might cause tear of the intact fibrotic capsule and dislocation of IOL. The capsule along the border of the optics might be a weak point against ocular massage.

Assessing the change of anisometropia in unilateral myopic children receiving monocular orthokeratology treatment.

BACKGROUND: This study aimed at comparing the inter-eye axial elongation difference in order to evaluate the change of anisometropia in unilateral myopic children wearing monocular orthokeratology (Ortho-K) lens. METHODS: In this retrospective cohort study, we recruited monocular myopic subjects treated with monocular Ortho-K lens from May 2012 to January 2017. The axial length (AL) of both eyes was recorded, and we calculated the AL difference as our primary outcome, to evaluate myopia progression. High anisometropia was defined as anisometropia more than 2.50D. The generalized estimating equations (GEE) model was used to assess the related risk factors. RESULTS: A total number of 31 unilateral myopic patients were identified. The initial wearing age of the subjects was 12.32+/-3.07 years. In myopic eyes, the initial spherical equivalent was -2.73+/-0.95 diopter (D). The mean follow-up duration was 2.01+/-1.48 years. A significant reduction in the AL difference was found, from 0.83+/-0.45 millimeters at the baseline to 0.59+/-0.49 millimeters at 24 months (P = 0.039). Besides, after wearing Ortho-K lens for a long term, high anisometropic wearers showed more AL difference reduction than low anisometropic wearers in unilateral myopic children (P=0.002). CONCLUSION: This study demonstrated that the myopic eyes in unilateral myopic children had less AL growth than the companion emmetropic eyes when treated with monocular Ortho-K lenses. Wearing Ortho-K lens for a long time would present a more significant AL difference reduction in high anisometropic children.

Angiotensin II does not influence expression of sarcoplasmic reticulum Ca2 + ATPase in atrial myocytes.

INTRODUCTION: The sarcoplasmic reticulum Ca(2+) ATPase (SERCA) is essential for the regulation of the intracellular calcium level in cardiomyocytes. Previous studies have found that angiotensin II (Ang II) decreased SERCA2 gene expression in ventricular myocytes. Alteration of SERCA activity is important in the mechanism of atrial fibrillation. The present study was undertaken to examine Ang II effects on atrial myocytes. MATERIALS AND METHODS: An approximately 1.75-kb promoter region of SERCA2 gene was cloned with the pGL3 luciferase vector. The direct effects of Ang II on SERCA2 gene expression in HL-1 atrial myocytes were examined by promoter activity assay, followed by Western blot analysis for protein levels and quantitative real-time reverse transcription polymerase chain reaction for mRNA amounts. RESULTS: Ang II did not increase the promoter activity of the 1,754-bp promoter-receptor construct of the SERCA2 gene. The levels of SERCA2 protein and mRNA were also unchanged at different time points after Ang II treatment. CONCLUSIONS: Although Ang II had prominent effects on SERCA2 in ventricular myocytes, it did not alter SERCA2 gene expression and protein levels in atrial myocytes. We provide a model for further investigation of the regulation of SERCA2 gene expression in atrial myocytes.

Waist-to-hip ratio correlates with homocysteine levels in male patients with coronary artery disease.

BACKGROUND: Obesity and homocysteine are important risk factors for cardiovascular disease. The relation between pattern of obesity and homocysteine is unclear. The objective of this study was to investigate the relation between pattern of obesity and plasma total homocysteine (tHcy) level in male patients with coronary artery disease (CAD). METHODS: A total of 63 male patients (mean age 66.2 years) with angiographically documented CAD were enrolled. Overnight fasting blood samples were measured for plasma tHcy, serum folic acid and serum vitamin B12 levels. Anthropometric measurements included waist-to-hip ratio (WHR) and body mass index (BMI). RESULTS: The mean WHR was 0.90+/-0.05, mean BMI 24.6+/-3.3 kg/m2 and the mean plasma tHcy level 11.6+/-3.2 micromol/L. In univariate analysis, plasma tHcy level correlated significantly with serum vitamin B12 level, serum folic acid level, WHR, estimated creatinine clearance, aspirin use and fibrate use. There was no significant association between plasma tHcy level and BMI. In multivariate analysis, only WHR (beta-value 22.263, p<0.001), serum level of vitamin B12 (beta-value -0.004, p=0.003), estimated creatinine clearance (beta-value -4.154, p=0.003) and use of fibrates (beta-value 2.307, p=0.031) were independent predictors of plasma tHcy level. CONCLUSIONS: WHR, but not BMI, is a strong independent predictor of plasma tHcy level in male patients with CAD.