Levels of anti-insulin antibodies in diabetic retinopathy patients: an observational cross-sectional study.

Aim: This study evaluated the levels of anti-insulin antibodies (AIAs) and the influence of some antidiabetic medications on AIA in diabetes mellitus (DM) patients with retinopathy. Patient & methods: An observational cross-sectional study. Results: A lower titer of AIA IgG was observed in the diabetic retinopathy (DR) and DM-only study categories compared with the control group [DR = 86 (5-560), DM-only = 50 (5-500), versus control = 200 (7-565); p = 0.017]. Taking nifedipine and metformin were negatively correlated (r = -0.32, p = 0.04) with the levels of AIA IgE in the DR group. Conclusion: A decreased titer of circulating AIAs was observed in the DR study category, suggesting that AIA may not contribute to the pathogenesis of DR.

Diabetic retinopathy (DR) is the main reason people lose their sight in countries with few resources. Anti-insulin antibodies, or AIAs, help the body fight off infections and may play a role in the development of DR. The study looked at how much AIA was in DR patients and how some diabetes drugs affected AIA levels. There was a negative link between nifedipine and one AIA (IgE) in people with DR, but a positive link between metformin and another AIA (IgG). AIA levels were lower in the DR study group, which suggests that AIA may not cause DR.

Vitreomacular interface abnormalities in the Ghanaian African.

BACKGROUND/OBJECTIVE: Describe vitreomacular interface abnormalities (VMIA) using spectral-domain optical coherence tomography (SD-OCT), and correlations with age-related macular degeneration (AMD) grade in Ghanaian Africans. SUBJECTS/METHODS: Prospective, cross-sectional study of adults aged ≥50 years recruited in Ghana AMD Study. Participant demographics, medical histories, ophthalmic examination, digital colour fundus photography (CFP) were obtained. High-resolution five-line raster OCT, Macular Cube 512 × 128 scans, and additional line scans in areas of clinical abnormality, were acquired. SD-OCT VMI features classified by International Vitreomacular Traction Study Group system and relationships to AMD grade were evaluated. OUTCOMES: VMIA prevalence, posterior vitreous detachment (PVD), vitreomacular adhesions (VMA), vitreomacular traction (VMT), epiretinal membranes (ERM), correlations with AMD grade. RESULTS: The full Ghana AMD cohort included 718 participants; 624 participants (1248 eyes) aged ≥50 years (range = 50-101, mean = 68.8), 68.9% female were included in this analysis. CFP with OCT scans were available for 776 eyes (397 participants); 707 (91.1%) had gradable CFP and OCT scans for both AMD and VMI grading forming the dataset for this report. PVD was absent in 504 (71.3%); partial and complete PVD occurred in 16.7% and 12.0% respectively. PVD did not increase with age (p = 0.720). VMIA without traction and macular holes were observed in 12.2% of eyes; 87.8% had no abnormalities. VMIA was not significantly correlated with AMD grade (p = 0.819). CONCLUSIONS: This provides the first assessment of VMIA in Ghanaian Africans. VMIA are common in Africans; PVD may be less common than in Caucasians. There was no significant association of AMD grade with VMIA.

Prospective identification of variables as outcomes for treatment (PIVOT): study protocol for a randomised, placebo-controlled trial of hydroxyurea for Ghanaian children and adults with haemoglobin SC disease.

BACKGROUND: Haemoglobin SC (HbSC) is a common form of sickle cell disease (SCD), especially among individuals of West African ancestry. Persons with HbSC disease suffer from the same clinical complications and reduced quality of life that affect those with sickle cell anaemia (HbSS/Sß0). Retrospective anecdotal data suggest short-term safety and benefits of hydroxyurea for treating HbSC, yet rigorous prospective data are lacking regarding optimal dosing, clinical and laboratory effects, long-term safety and benefits, and appropriate endpoints to monitor. Prospective Investigation of Variables as Outcomes for Treatment (PIVOT) was designed with three aims: (1) to measure the toxicities of hydroxyurea treatment on laboratory parameters, (2) to assess the effects of hydroxyurea treatment on sickle-related clinical and laboratory parameters, and (3) to identify study endpoints suitable for a future definitive phase III trial of hydroxyurea treatment of HbSC disease. METHODS: PIVOT is a randomised, placebo-controlled, double blind clinical trial of hydroxyurea. Approximately 120 children and 120 adults ages 5-50 years with HbSC disease will be enrolled, screened for 2 months, and then randomised 1:1 to once-daily oral hydroxyurea or placebo. Study treatment will be prescribed initially at 20 ± 5 mg/kg/day with an opportunity to escalate the dose twice over the first 6 months. After 12 months of blinded study treatment, all participants will be offered open-label hydroxyurea for up to 4 years. Safety outcomes include treatment-related cytopenias, whole blood viscosity, and adverse events. Efficacy outcomes include a variety of laboratory and clinical parameters over the first 12 months of randomised treatment, including changes in haemoglobin and fetal haemoglobin, intracranial arterial velocities measured by transcranial Doppler ultrasound, cerebral oxygenation using near infrared spectrometry, spleen volume and kidney size by ultrasound, proteinuria, and retinal imaging. Exploratory outcomes include functional erythrocyte analyses with ektacytometry for red blood cell deformability and point-of-sickling, patient-reported outcomes using the PROMIS questionnaire, and 6-min walk test. DISCUSSION: For children and adults with HbSC disease, PIVOT will determine the safety of hydroxyurea and identify measurable changes in laboratory and clinical parameters, suitable for future prospective testing in a definitive multi-centre phase III clinical trial. TRIAL REGISTRATION: PACTR, PACTR202108893981080. Registered 24 August 2021, https://pactr.samrc.ac.za.

Characterization of West African Crystalline Macular Dystrophy in the Ghanaian Population.

OBJECTIVE: West African crystalline maculopathy (WACM) is characterized by the presence of macular hyperrefractile crystal-like deposits. Although the underlying pathophysiology has not been elucidated, a few biologic drivers have been proposed. We analyzed a large WACM case series to gain a more robust understanding of its features and etiology. DESIGN: Prospective, cross-sectional cohort study. SUBJECTS: Participants with WACM were selected from the large cohort recruited in the Ghana Age-Related Macular Degeneration Study. METHODS: Demographic and detailed medical histories, full ophthalmic examinations, digital color fundus photographs, and OCT images were obtained. All cases with WACM were evaluated by 3 retina experts. Crystal numbers, location, and distribution were determined. Associations between WACM and White age-related macular degeneration (AMD) risk variants were assessed using Firth's bias-reduced logistic regression, including age and sex as covariates. MAIN OUTCOME MEASURES: Phenotypic features of, and genetic associations with, WACM. RESULTS: West African crystalline maculopathy was identified in 106 eyes of 53 participants: 22 were bilateral and 24 were unilateral. Grading for AMD was not possible in 1 eye in 7 participants with WACM; therefore, laterality was not assessed in these subjects. Thirty-eight participants were women and were 14 men; sex was unrecorded for 1 participant. The mean age was 68.4 years (range, 45-101 years). Typical WACM crystals were demonstrated on OCT, which were more easily identified at high contrast and predominantly located at the inner limiting membrane. In eyes with copathology, crystals localized deeper in the inner retina, with wider retinal distribution over copathology lesions. There was no association with age or sex. A significant association was observed between the complement factor H (CFH) 402H risk variant and WACM. CONCLUSIONS: This study confirms the localization of crystals adjacent to the inner limiting membrane and distribution over lesions in eyes with copathology. The evaluation of OCT images under high contrast allows improved identification. West African crystalline maculopathy may be associated with the CFH-CFHR5 AMD risk locus identified among Whites; however, it is also possible that the combination of crystals and the CFH 402H allele increases the risk for developing late AMD. Further analyses using larger sample sizes are warranted to identify causalities between genotype and WACM phenotype.

Utilization of eye health services and diabetic retinopathy: a cross-sectional study among persons living with diabetes visiting a tertiary eye care facility in Ghana.

BACKGROUND: There have been a major advance made in screening, early diagnosis, and prompt treatment of Diabetic Retinopathy among Person living with diabetes (PLWD). However, screening services remain a challenge in Low-Middle-Income-Countries where access to eye care professionals is inadequate. This study assesses the utilization of Eye Health Service prevalence (UEHS) among PLWD and associated factors and further quantifies its association with Non-Proliferative Diabetic Retinopathy (NPDR). METHODS: A cross-sectional study design with a random sample of 360 PLWD was conducted at Korle-Bu Teaching Hospital, a National Referral Centre in Ghana from May to July 2019. UEHS and DR were the study outcomes. We adopted Poisson and Probit regression analysis to assess factors associated with UEHS over the past year. We employed pairwise and phi correlation (fourfold correlational analysis) to assess the relationship between UEHS and DR (ordinal and binary respectively). Ordered Logistic and Poisson regression were applied to assess the association between the UEHS and DR. Stata 16.1 was used to perform the analyses and a p-value ≤ 0.05 was deemed significant. RESULTS: The prevalence of UEHS over the past year and DR was 21.7 %(95 %CI = 17.7-26.2) and 65.0 %(95 %CI = 59.9-69.8 respectively. The prevalence of severe NPDR with Clinically Significant Macular Edema (CSME) was 23.9 %(19.8-28.6). Type of diabetes, increasing age, educational level, mode of payment for healthcare services, marital status, years since diagnosis, and current blood glucose significantly influenced UEHS. There was a negative relationship between DR and UEHS (Pairwise and φ correlation were - 20 and - 15 respectively; p < 0.001). Non-UEHS among PLWD doubles the likelihood of experiencing severe NPDR with CSME compared with UEHS among PLWD [aOR(95 %CI) = 2.05(1.03-4.08)]. Meanwhile, the prevalence of DR among patients per non-UEHS was insignificantly higher [12 %; aPR(95 %CI) = 0.89-1.41)] compared with patients who utilized eye care health service. CONCLUSIONS: Most of the PLWD did not utilize the eye health service even once in a year and that was highly influenced by type of diabetes and increasing age. Type 2 diabetes patients and middle age decreased the likelihood of UEHS. There was a negative relationship between DR and UEHS among PLWD and this doubled the likelihood of experiencing severe NPDR with CSME. Structured health education and screening interventions are key to improving UEHS.

Safety of intravitreal ziv-aflibercept in choroido-retinal vascular diseases: A randomised double-blind intervention study.

AIM: To evaluate the safety of 1.25mg and 2mg intravitreal ziv-aflibercept (IVZ) in Ghanaian eyes with choroido-retinal vascular diseases. DESIGN: Prospective, randomised, double blind, interventional study. METHODS: Twenty patients with centre involving macular oedema in diabetic retinopathy, retinal vein occlusion, and neovascular age-related macular degeneration were assigned to 2 groups receiving 3 doses of 1.25mg/0.05ml (group 1) and 2mg/0.08ml IVZ (Group 2) at 4 weekly intervals. Safety data was collected after 30 minutes, 1 and 7 days, and 4, 8 and 12 weeks after injection. Changes in continuous variables were compared using paired t-test and categorical variables were compared using chi-square test of proportions. Repeated-Measures ANOVA with nesting test was used to compare variations in continuous variables by IVZ dose over time. Primary outcome measures were ocular and systemic adverse events at 4 weeks. RESULTS: Eleven females and nine males, with mean age of 63.2± 7.3 years were included. Ocular adverse events included subconjunctival haemorrhage in 1 eye, intraocular pressure (IOP) >21mmHg at 30 minutes in 6 eyes and mild pain in 3 eyes at 1-day. There was no significant difference in IOP rise between the 2 groups at 30 minutes (p = 0.21). No other ocular or systemic adverse events were observed. There was significant improvement in the best corrected visual acuity (LogMAR) from 0.95±0.6 to 0.6±0.4 (p<0.01) and 0.47±0.3 (p<0.01), reduction in central subfield foveal thickness from 405.9±140 um at baseline to 255.6±75 um (p<0.01) and 238±88 um (p<0.01) at 4 and 12 weeks respectively, although no difference was observed between the 2 groups (p = 0.34). CONCLUSION: IVZ at 1.25mg and 2mg had similar safety profiles, and did not have any major unexpected adverse events. Further studies with larger cohorts are required to confirm efficacy.

Case series of six patients diagnosed and managed for idiopathic intracranial hypertension at a tertiary institution eye centre.

BACKGROUND: Idiopathic Intracranial Hypertension (IIH) occurs secondary to raised intracranial pressure (ICP) of unknown etiology and is diagnosed when all other causes of raised ICP have been excluded. It can leave devastating sequelae such as permanent visual loss, hence the need for timely diagnosis and treatment. Anecdotally, one or two cases of idiopathic intracranial hypertension (IIH) previously presented at the Eye Centre, KBTH yearly. However, six cases were seen within a 6-month period, prompting the need to study the clinical features of IIH in this population. OBJECTIVE: We aim to evaluate the clinical features of patients presenting with IIH at KBTH. METHODOLOGY: This is a retrospective case series with contemporaneous collection of data of six patients who presented to the Eye Centre (KBTH) between October 2016 and March 2017 with clinical features suggestive of IIH. The patients were evaluated and diagnosed based on clinical judgement as well as using the modified Dandy criteria. RESULTS: All six patients were female and all except one were obese. The age range was 8 to 40 years with median 22.5 years. Symptoms in the 8-year-old were preceded by oral doxycycline for acne treatment. One patient had a history of using oral contraceptive pills prescribed for irregular menses. Clinical features of blurred vision, headache, and papilloedema were relieved with oral acetazolamide. CONCLUSION: The upsurge of IIH may be due to the increased incidence of obesity in Ghana. Timely diagnosis and treatment is needed to avoid irreversible blindness. FUNDING: None.

Corneal collagen cross-linking for treating keratoconus.

BACKGROUND: Keratoconus is a condition of the eye that affects approximately 1 in 2000 people. The disease leads to a gradual increase in corneal curvature and decrease in visual acuity with consequent impact on quality of life. Collagen cross-linking (CXL) with ultraviolet A (UVA) light and riboflavin (vitamin B2) is a relatively new treatment that has been reported to slow or halt the progression of the disease in its early stages. OBJECTIVES: The objective of this review was to assess whether there is evidence that CXL is an effective and safe treatment for halting the progression of keratoconus compared to no treatment. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 7), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to August 2014), EMBASE (January 1980 to August 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to August 2014), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to August 2014), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organisation International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We used no date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 28 August 2014. SELECTION CRITERIA: We included randomised controlled trials (RCTs) where CXL with UVA light and riboflavin was used to treat people with keratoconus and was compared to no treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results, assessed trial quality, and extracted data using standard methodological procedures expected by Cochrane. Our primary outcomes were two indicators of progression at 12 months: increase in maximum keratometry of 1.5 dioptres (D) or more and deterioration in uncorrected visual acuity of more than 0.2 logMAR. MAIN RESULTS: We included three RCTs conducted in Australia, the United Kingdom, and the United States that enrolled a total of 225 eyes and analysed 219 eyes. The total number of people enrolled was not clear in two of the studies. Only adults were enrolled into these studies. Out of the eyes analysed, 119 had CXL (all using the epithelium-off technique) and 100 served as controls. One of these studies only reported comparative data on review outcomes. All three studies were at high risk for performance bias (lack of masking), detection bias (only one trial attempted to mask outcome assessment), and attrition bias (incomplete follow-up). It was not possible to pool data due to differences in measuring and reporting outcomes. We identified a further three unpublished trials that potentially had enrolled a total of 195 participants.There was limited evidence on the risk of progression. Analysis of the first few participants followed up to one year in one study suggested that eyes given CXL were less likely to have an increase in maximum keratometry of 1.5 D or more at 12 months compared to eyes given no treatment, but the confidence intervals (CI) were wide and compatible with no effect or more progression in the CXL group (risk ratio (RR) 0.12, 95% CI 0.01 to 2.00, 19 eyes). The same study reported the number of eyes with an increase of 2 D or more at 36 months in the whole cohort with a RR of 0.03 favouring CXL (95% CI 0.00 to 0.43, 94 eyes). Another study reported "progression" at 18 months using a different definition; people receiving CXL were less likely to progress, but again the effect was uncertain (RR 0.14, 95% CI 0.01 to 2.61, 44 eyes). We judged this to be very low-quality evidence due to the risk of bias of included studies, imprecision, indirectness and publication bias but noted that the size of the potential effect was large.On average, treated eyes had a less steep cornea (approximately 2 D less steep) (mean difference (MD) -1.92, 95% CI -2.54 to -1.30, 94 eyes, 1 RCT, very low-quality evidence) and better uncorrected visual acuity (approximately 2 lines or 10 letters better) (MD -0.20, 95% CI -0.31 to -0.09, 94 eyes, 1 RCT, very low-quality evidence) at 12 months. None of the studies reported loss of 0.2 logMAR acuity. The data on corneal thickness were inconsistent. There were no data available on quality of life or costs. Adverse effects were not uncommon but mostly transient and of low clinical significance. In one trial, 3 out of 12 participants treated with CXL had an adverse effect including corneal oedema, anterior chamber inflammation, and recurrent corneal erosions. In one trial at 3 years 3 out of 50 participants experienced adverse events including mild diffuse corneal oedema and paracentral infiltrate, peripheral corneal vascularisation, and subepithelial infiltrates and anterior chamber inflammation. No adverse effects were reported in the control groups. AUTHORS' CONCLUSIONS: The evidence for the use of CXL in the management of keratoconus is limited due the lack of properly conducted RCTs.

Rare case of post-cataract-surgery Prevotella endophthalmitis diagnosed by polymerase chain reaction DNA sequencing.

We report the presentation, diagnosis, and management of endophthalmitis caused by the opportunistic Prevotella species. The case was referred to us following uneventful phacoemulsification and intraocular lens implantation. Accurate identification of this rare cause of endophthalmitis was made using bacterial polymerase chain reaction DNA sequencing. Subsequent prompt modification of antibacterial therapy allowed resolution of signs and symptoms and significant visual recovery. To our knowledge, this is the first reported case of diagnosis and management of post-cataract-surgery endophthalmitis caused by the opportunistic Prevotella species.

Ten-year experience of pulsed intravenous cyclophosphamide and methylprednisolone protocol (PICM protocol) in severe ocular inflammatory disease.

AIMS: Severe ocular inflammation is a blinding ophthalmological emergency. This study evaluates the efficacy and patient tolerance of a validated regime of pulsed intravenous cyclophosphamide and methylprednisolone ('PICM protocol') for these patients. METHODS: 26 patients with severe inflammatory eye disease (43 eyes: 22 uveitis, 21 scleritis/sclerokeratitis; median age 52 years (IQR 40.25-62.25)) presenting to a regional tertiary referral centre were recruited over a 10-year period (January 2002-December 2011) into the PICM protocol, comprising intravenous cyclophosphamide 15 mg/kg, intravenous methylprednisolone 10 mg/kg, maximum nine pulses over 20 weeks supplemented with low-dose continuous oral prednisolone. Data were captured pretreatment and at 6 and 12 months follow-up. Primary outcome measures were control of inflammation according to standard criteria and reduction in systemic glucocorticoid to ≤10 mg prednisolone/day. RESULTS: A median of six pulses (IQR 5-6) were administered over a median of 3 months (IQR 2.25-4). In the scleritis/sclerokeratitis group, 15/21(71%) achieved success or partial success at 6 and 12 months versus 9/22 (41%) for the same time points in the uveitis group (χ(2)=4.058, p=0.044). Two patients had adverse events requiring treatment withdrawal. CONCLUSIONS: This PICM protocol is a well-tolerated regimen for managing severe ocular inflammation and appears particularly useful in patients with scleritis/sclerokeratitis.

High rate of incomplete resection after primary excision of eyelid BCC: multi-staged resection rarely needs more than two procedures.

PURPOSE: Small, well-demarcated, biopsy-proven periocular basal cell carcinomas (BCC) are often excised in a single stage with immediate reconstruction when histology or location is considered low-risk. We investigated margin clearance in patients undergoing primary excision and immediate reconstruction (PER) versus multi-staged fast paraffin excision (MSE) and reviewed risk factors for incomplete excision. METHODS: Retrospective, interventional, comparative case series of periocular BCCs excised over a 3-year period (2006-2008). RESULTS: Ninety consecutive patients with periocular BCC (average age 77 ± 10.1 years, 60% females) were included. 39% (35/90) underwent PER with the remainder managed by MSE (55/90, 61%). Patients undergoing MSE had larger lesions (38% > 10 mm versus 23% PER) which were more likely to involve the medial canthus (25 versus 11% PER). Incomplete histological clearance was noted in 34% (12/35) patients after PER. Only 3/55 (5%) needed third stage of excision in the MSE group with final incomplete excision in two cases (3.6%) that did not undergo a third stage excision. No significant risk factors were found likely to predict residual BCC overall, after first excision stage. Subgroup analysis for patients undergoing PER showed multiple lesions as the only statistically significant factor for incomplete excision. CONCLUSION: This study shows an unacceptably high rate of incomplete resection with primary excision and repair using a standard 3 mm margin. The majority of lesions undergoing multi-stage excision required no more than two stages for complete removal. Multi-stage excision with histological confirmation of clear margins prior to reconstruction is recommended for routine management of all periocular BCC.

Beware the ornamental plant.

A keen female gardener presented to the emergency department of the hospital with a large corneal abrasion, conjunctival injection, an anterior chamber reaction and a hypopyon. She put it down to trauma that day while gardening, as she had been pruning her patio plant. The Euphorbia species of ornamental plants have been known to cause an intense reactive anterior uveitis and kerato-conjunctivitis caused by the milky sap it produces. Emergency medicine doctors and ophthalmologists should be aware of the effects of the sap of the Euphorbia species of plants.