Ten-year mortality and long-term visual acuity outcomes in patients with exudative age-related macular degeneration treated with intravitreal anti-vascular endothelial growth factor injections.

PURPOSE: There are limited real-world data on long-term mortality and visual outcomes in patients treated with anti-vascular endothelial growth factor (VEGF) for exudative age-related macular degeneration (exudative AMD). We assessed 10-year mortality and clinical outcomes in exudative AMD patients treated with intravitreal therapy (IVT) anti-VEGF injections on a pro-re-nata (PRN) regime following a standard loading regime. METHODS: Retrospective cohort study of the first 216 exudative AMD patients receiving IVT anti-VEGF for exudative AMD at a public tertiary referral hospital in Scotland. Main outcome measures were mortality, cause of death and best-corrected visual acuity (BCVA). RESULTS: A total of 216 patients were included. Mean age at presentation was 79.1 years [standard deviation (SD) 6.9]. Mean follow-up duration was 6.6 years (SD 3.2) during which there was a mean 24.3 Early Treatment Diabetic Retinopathy Study (ETDRS) letter loss in BCVA (P < 0.0001). Patients received a mean of 2.2 (SD 1.8) injections per year of follow-up. Overall, 52.6% (113/216) died during the period studied. Observed annual mortality incidence risk was 6.5% (SD 3.1) and was found to be significantly lower (P = 0.0064) than the expected annual death incidence risk (9.6%, SD 1.5) based on age and sex standardised Scottish mortality risk. The most common causes of death were malignancies (21.3%) and infection (20.0%). CONCLUSIONS: This study highlights the relatively good long-term prognosis in vision and mortality in exudative AMD treated with a PRN regime in the real world. Although the majority lost vision, the rate of decline was significantly slower than that which would have been experienced in the pre-anti-VEGF era and reassuringly standardised mortality risk was lower than the national average.

Novel biallelic USH2A variants in a patient with usher syndrome type IIA- a case report.

BACKGROUND: Usher Syndrome is the commonest cause of inherited blindness and deafness. The condition is clinically and genetically heterogeneous, with no current treatment. We report a case carrying novel biallelic variants in USH2A causing progressive early adolescent onset visual and hearing impairment consistent with Usher Syndrome Type IIA. CASE PRESENTATION: Our patient presented at age 13 with progressive visual field loss and hearing loss, associated with early onset of cataract in her 40s requiring lens extraction. Now 52 years old, latest best corrected visual acuity (BCVA) stands at Logmar Right Eye (RE) 0.8 and Left Eye (LE) 0.2, with significantly constricted visual fields bilaterally. She was registered partially sighted age 46. Clinical and molecular genetic assessment of the proband was consistent with a diagnosis of Usher Syndrome Type IIA. Genetic testing identified two novel USH2A variants, resulting in the premature termination codon p.Leu30Ter and a missense mutation p.Cys3251Tyr. Segregation analysis confirmed that these variants were biallelic in the affected case. Comprehensive in silico analysis confirmed that these mutations are the probable cause of Usher Syndrome Type IIA in this individual. CONCLUSIONS: The identification of novel mutations in USH2A increases the spectrum of genetic variations that lead to Usher Syndrome, aiding genetic diagnosis, assessment of patient prognosis, and emphasising the importance of genetic testing to identify new mutations in patients with undiagnosed progressive visual loss.

Depression secondary to vision loss in old age and an effective rapid screening tool for undiagnosed cases.

BACKGROUND: Zenebe et al. recently stated that despite depression being a common mental health problem in the elderly population, it is underdiagnosed in over half of the cases (Zenebe et al. in Ann Gen Psychiatry, 2021). They described an extensive list of risk factors associated with geriatric depression. However, we noted that they did not include ophthalmic conditions in this list which have previously been identified as an important risk factor for depression in the elderly. MAIN BODY: To determine the extent of undiagnosed anxiety and depression in our elderly population with vision loss, we screened a cohort of our patients, over 60 years with vision loss secondary to macular disease for both conditions. Our cohort included 104 patients with mean best corrected visual acuity 0.58 LogMAR (Snellen equivalent 6/24). In this group, we identified 29.8% (31/104) and 28.8% (30/104) of patients with at least one depression or anxiety-related symptom, respectively, in the past 2 weeks. We identified 7.7% (8/104) and 3.8% (4/104) who had significant symptoms of depression and anxiety, respectively, that warranted further follow-up. Only two of these patients had previously been diagnosed with anxiety or depression with the majority having no previous history of either condition. Patients from our cohort who screened for depression or anxiety often cited frustration completing tasks and loss of independence secondary to declining vision. They also complained that the vision loss resulted in a lack of confidence which in turn resulted in social isolation and loneliness. Most of the patients welcomed referral to their GP for follow-up for input regarding their mental health and they also stated an interest in attending hospital optometry low vision services and counselling support. CONCLUSIONS: With increasing time pressures on healthcare services and the rising use of virtual clinics especially during the COVID-19 pandemic, it is still essential to screen efficiently for depression in those elderly patients who are at significant risk. There is a considerable burden of major depressive disease in the geriatric population, and we would recommend that physicians (Geriatricians, GPs, Ophthalmologists etc.) screen elderly patients with vision loss for depression using the rapid screening tool which we suggest.

Clinical outcomes of switching to aflibercept using a pro re nata treatment regimen in patients with neovascular age-related macular degeneration who incompletely responded to ranibizumab.

BACKGROUND: To assess the effect of switching patients previously incompletely treated with ranibizumab (RBZ) to aflibercept (AFL) using a pro re nata (PRN) treatment strategy in neovascular age-related macular degeneration (nvAMD). METHODS: A retrospective case series was conducted on patients who had persistent or recurrent intra- and/or sub-retinal fluid treated initially with RBZ and subsequently switched to AFL. The main outcome measures were best corrected visual acuity (BCVA) and central retinal thickness (CRT) measured at different stages of the study. Friedman analysis of variance and Wilcoxon test were used to examine differences in BCVA and CRT. RESULTS: Two hundred and seven eyes from 182 patients were included. BCVA and CRT improved significantly initially following 3 RBZ injections with a mean gain of 3.7 letters (p < 0.001) and a mean loss of 69 µm (p < 0.001) respectively. Following PRN RBZ therapy and immediately prior to switching to AFL (mean 129 weeks), there was a mean loss of 6.7 letters (p < 0.001) BCVA and a mean gain of 24 µm (p < 0.001) CRT. AFL loading resulted in a mean improvement of 0.7 letters (p = 0.28) BCVA and 55 µm (p < 0.001) CRT. At final follow-up following AFL PRN therapy (mean 85 weeks), there was a mean loss of 8.9 letters (p < 0.001) BCVA and a mean gain of 12 µm (p < 0.05) CRT. CONCLUSION: AFL loading resulted in a significant anatomical improvement but no significant change in visual acuity. However, the benefits of switching were gradually lost over time with AFL PRN dosing despite an increased injection rate when compared with RBZ PRN treatment. TRIAL REGISTRATION: Not applicable.

Patients' Perception of Robot-Driven Technology in the Management of Retinal Diseases.

INTRODUCTION: There is increasing application of robots and other artificial intelligence-driven technologies in the management of retinal disease. These technologies have the potential to meet increasing demands for retinal diseases. However, there is currently a lack of understanding of patients' attitudes towards use of robots in ophthalmology. This study investigates patients' attitudes towards robot-led management of retinal disease. METHODS: Paper questionnaires were distributed to 177 patients attending intravitreal treatment (IVT) at the Princess Alexandra Eye Pavilion between 1 October 2022 and 31 January 2023. The questionnaire collected information on age, sex, diagnosis and postcode. In the questionnaire, patients responded to questions about their attitudes towards robot-led diagnosis, treatment decisions and IVT injections. Responses were collected using a 5-category Likert scale which was analysed using ordinal logistic regression with adjustments for age, sex and deprivation status. RESULTS: Those from affluent socioeconomic backgrounds were significantly (p < 0.001) more accepting of robots diagnosing and deciding on treatment, although the total number of patients who were accepting was only 26 (14.7%). Furthermore, there was an increased proportion of patients who would accept robots if the robot made fewer mistakes than doctors, if the robot reduced waiting or appointment time and if the robot was able to communicate well and have empathy; the same association with socioeconomic background remains (p < 0.001). Lastly, 116 patients (65.5%) would not be happy if IVT injections were performed by a robot; this was more likely the case if the patient was female (p = 0.04) or from a more deprived socioeconomic background (p < 0.001). CONCLUSION: Attitudes towards robot involvement in diagnosis and management of retinal disease are significantly associated with socioeconomic backgrounds and sex. Additional studies are required to further investigate these determinants of robot receptiveness to ensure acceptance and compliance with treatment with these new technologies.

Practical implementation of a q4-q16 aflibercept treat-and-extend pathway for the treatment of neovascular age-related macular degeneration: Updated guidance from a UK expert panel.

OBJECTIVES: This report, based on guidance from a panel of UK retina specialists, introduces a revised intravitreal aflibercept (IVT-AFL) treat-and-extend (T&E) pathway for the treatment of neovascular age-related macular degeneration (nAMD). The T&E pathway incorporates the updated IVT-AFL label (April 2021) allowing flexible treatment intervals of 4 weeks to 16 weeks, after three initiation doses and a further dose after 8 weeks. Practical guidance is provided on the clinical implementation of the revised pathway, with the aim of supporting clinical decision-making to benefit patients and addressing capacity issues in nAMD services. METHODS: Three structured round-table meetings of UK retina specialists were held online on 19 May, 16 June and 13 October 2021. These meetings were organised and funded by Bayer. RESULTS: The authors revised the previously published consensus pathway to reflect the changes to the IVT-AFL label and developed guidelines for the implementation of the pathway in UK clinical practice. The guidelines include topics such as recommendations for extending patients with 2- or 4-week adjustments, extending patients to 16-week treatment intervals, managing fellow eye involvement, and reducing treatment intervals for patients with particularly active disease. CONCLUSIONS: The revised IVT-AFL T&E nAMD pathway offers guidance to clinicians seeking to increase the dosing flexibility of IVT-AFL, with 4- to 16-week treatment intervals, in line with the updated IVT-AFL label, to meet the continually evolving demands of nAMD service provision.

Proptosis as the presenting sign of giant prolactinoma in a prepubertal boy: successful resolution of hydrocephalus by use of medical therapy.

We report the case of a 13-year-old prepubertal boy who presented with a left-sided proptosis, bilateral papilloedema and hydrocephalus who was subsequently diagnosed with a giant prolactinoma invading the left orbit. He was commenced on dopamine receptor agonists in the form of quinagolide and cabergoline, and made an excellent response to medical therapy alone, with resolution of hydrocephalus, restoration of normal vision and a 98% reduction in serum prolactin. The rapid improvement achieved negated the requirement for surgery and this highlights the efficacy of the dopamine agonists in the management of giant prolactinomas, even in the presence of neurological symptoms.

Relationship of smoking and cardiovascular risk factors with polypoidal choroidal vasculopathy and age-related macular degeneration in Chinese persons.

PURPOSE: Polypoidal choroidal vasculopathy (PCV) has been described as a distinct clinical entity from choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). The present study aimed to determine risk factors for PCV and to compare associations with those for CNV secondary to AMD. DESIGN: Case-control study. PARTICIPANTS: Patients of Chinese ethnicity with clinically and angiographically diagnosed PCV (n = 123) or CNV secondary to AMD (n = 128) were recruited from a tertiary eye hospital in Singapore. Controls without signs of PCV, CNV secondary to AMD, or other retinal pathologic features (n = 1489) were selected from a population-based study. METHODS: Patients underwent an ophthalmologic examination including digital color fundus photography, stereoscopic fluorescein angiography (FA), and indocyanine green angiography (ICGA). Classification into PCV or CNV secondary to AMD was based on FA and ICGA findings. Risk factors were determined from a standardized interview, with blood pressure recorded using a digital automatic blood pressure monitor. MAIN OUTCOME MEASURES: Polypoidal choroidal vasculopathy or CNV secondary to AMD. RESULTS: Persons who smoked were more likely to have PCV (39.9% vs. 13.4%) or CNV secondary to AMD (45.0% vs. 12.3%) than those who did not smoke. After controlling for age, gender, diabetes, hypercholesterolemia, and hypertension, persons who smoked were 4 times more likely to have PCV (odds ratio [OR], 4.4; 95% confidence interval [CI], 2.5-7.7; P<0.001) and CNV secondary to AMD (OR, 4.9; 95% CI, 2.7-8.8; P<0.001). A significant, negative association also was found between diastolic blood pressure and CNV secondary to AMD (OR, 0.7; 95% CI, 0.5-0.9; P = 0.017, adjusted for age, gender, smoking, diabetes, and hypercholesterolemia), but diastolic blood pressure was not associated with PCV. CONCLUSIONS: Smoking but not other vascular risk factors is significantly associated with both PCV and CNV secondary to AMD in Chinese persons. The similarity of associations suggests that there may be common risk factors and pathological mechanisms.

Toll-like receptor 3 polymorphism rs3775291 is not associated with choroidal neovascularization or polypoidal choroidal vasculopathy in Chinese subjects.

BACKGROUND/AIMS: Age-related macular degeneration (AMD) is a leading cause of visual impairment. A single-nucleotide polymorphism (SNP; rs3775291) in the Toll-like receptor 3 (TLR3) gene has recently been implicated in the pathogenesis of AMD in Caucasian populations. The aim of this study was to examine this association in Chinese persons with choroidal neovascularization (CNV) secondary to AMD and polypoidal choroidal vasculopathy (PCV). METHODS: This was an observational cross-sectional study in Singapore. Study subjects were of Chinese ethnicity and included patients with exudative maculopathy and normal control subjects. The diagnoses of CNV and PCV were made based on fundus examination, fluorescein angiography and indocyanine green angiography findings. Genomic DNA was extracted, and genotypes were determined by bidirectional DNA sequencing. We compared the allele and genotype frequencies between subjects with CNV and PCV with controls using the software PLINK. RESULTS: A total of 246 subjects with exudative maculopathy (consisting of 126 with CNV and 120 with PCV) and 274 normal control subjects were recruited. The distribution of rs3775291 SNP genotypes for CNV and PCV was not significantly different from that for normal controls. CONCLUSION: This study indicates that the TLR3 rs3775291 gene polymorphism is not associated with CNV and PCV in Singaporean Chinese patients.

Choroidal neovascularisation in a predicted female choroideraemia carrier treated with intravitreal anti-vascular endothelial growth factor.

PURPOSE: To report a case of choroidal neovascularisation and leakage in a myopic female predicted to be a choroideraemia carrier treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF). METHODS: Case report. RESULTS: A female magazine editor presented with sudden decrease in vision in her right eye, with Snellen visual acuities (VAs) of 1/60 and 3/60 in the right and left eyes respectively. She was diagnosed with choroidal neovascularisation (CNV) formation and subretinal haemorrhage in her right eye. This is on a background of previous presentations, the first of which was 20 years ago for declining left eye vision. She was subsequently found to be a predicted choroideraemia carrier. However, she also has high myopia, and it is unclear whether the predicted choroideraemia carrier status or high myopia is the main underlying cause of her CNV, although we believe that the former is more likely. The first episode of CNV in her right eye was treated successfully with intravitreal anti-VEGF. However, she experienced four further CNV reactivations in her right eye, all of which were treated successfully with anti-VEGF. At her last follow-up visit to date, Snellen VAs were 6/9 and 3/60 in her right and left eye respectively. CONCLUSION: This is a unique case of CNV formation in a predicted choroideraemia carrier who also has co-existent high myopia. Prompt treatment of CNV activity with anti-VEGF has been efficacious in prevention of subretinal fibrosis and irreversible vision loss and allowed the patient to continue working in her chosen career.

The Eye in Forensic Medicine: A Narrative Review.

ABSTRACT: The eye, with its distinctive anatomy, not only reflects a wide variety of diseases in life but also undergoes a myriad of post-mortem changes. Consequently, the eye has long been an area of interest in forensic science, primarily for the estimation of post-mortem interval and therefore the time of death and also for assistance in ascertaining the cause of death. There has been significant progress in the knowledge of ophthalmic forensic science using new technologies which have allowed further possibilities to arise where understanding of this field can assist the forensic pathologist. This review aims to highlight the current knowledge which exists in this field and also to identify important avenues for further investigation. Post-mortem changes of the eye along with its current applications and challenges will be discussed. These include the important areas of post-mortem iris biometrics, pupil size correlation with post-mortem interval, use of point-of-care technology on vitreous humor, and the use of ophthalmic imaging in pediatric abusive head trauma.

A classification system for polypoidal choroidal vasculopathy.

PURPOSE: To describe the demographic features and clinical characteristics of polypoidal choroidal vasculopathy (PCV) in Chinese patients and define a new classification system. METHODS: Retrospective review of 138 eyes of 123 patients presenting to the Singapore National Eye Center with PCV. Patients underwent ophthalmologic examination including digital color fundus photography and stereoscopic indocyanine green angiography. Classification based on indocyanine green angiography findings. RESULTS: Mean age of patient 68.3 years and 62.4% were men. PCV was unilateral in 87.8% cases and age-related maculopathy was present in the unaffected fellow eye in 22.8%. Average largest size of polyp was 207 microm. PCV lesions were found in multiple discrete areas in 34.8%. Formation of lesion was cluster in 66.7%, single in 27.5%, and string in 5.8%. PCV lesions were found in the extrafoveal area in 63.0%, subfoveal in 29.7%, juxtafoveal in 15.9%, and peripapillary in 8.0%. CONCLUSIONS: Demographics of PCV, unilaterality and frequency of age-related maculopathy in fellow eye similar to other reports in Asians. We describe a classification system for PCV comprising polyp size, location, formation, and number of discrete polyp areas, which can be used for prospective interventional clinical studies and may aid in future prognosis and management of this condition.

Unilateral retinitis pigmentosa occurring in an individual with a mutation in the CLRN1 gene.

This case report depicts the clinical course of a female patient with unilateral retinitis pigmentosa, who first presented at the age of 12 years. Fundus photography at the time revealed unilateral pigmentary retinopathy, which was associated with extinguished electroretinogram (ERG) signal. At 35 years of age, fundus examination revealed deterioration of pre-existing unilateral pigmentary retinopathy with progressive visual field defect detected on Goldmann visual field testing. ERG findings remained unchanged and multifocal ERG showed unilateral decrease in amplitude in the affected eye. The patient was referred for genetic counselling. Next-generation sequencing identified a deleterious heterozygous c.118T>G (p.Cys40Gly) mutation in the CLRN1 gene.

Nystagmus secondary to drug exposure in utero.

AIM: To report the occurrence of nystagmus in children exposed to opiates and/or benzodiazepines during pregnancy, and to describe the associated ocular and systemic findings. METHODS: Clinical examination and casenote review of 14 children with nystagmus whose mothers had misused opiates and/or benzodiazepines during pregnancy. RESULTS: Twelve children were exposed to opiates during pregnancy, of whom nine had also been exposed to benzodiazepines. Two children were exposed to benzodiazepines alone. In the primary position, the nystagmus was a fine horizontal pendular type in 10 (71.4%) children and was a fine horizontal jerk nystagmus in the other 4 (28.6%) children. The onset of the nystagmus probably occurred in the first 6 months of life in all cases. The mean binocular best-corrected logarithm of the minimum angle of resolution visual acuity was 0.59 (20/80). Electroretinogram and visual evoked potential examinations were found to be normal in the three children tested. Nine (64.3%) children had developmental delay and at least 7 (50%) had delayed visual maturation. Six children had microcephaly and two had bilateral optic nerve hypoplasia. None of the children had a specific neurological diagnosis or seizure disorder. CONCLUSION: This study strongly supports a teratogenic association between exposure to controlled drugs in utero and infantile nystagmus. Furthermore, the nystagmus and associated clinical features seem to be particularly associated with combined use of opiates and benzodiazepines. Exposure to opiates and/or benzodiazepines during pregnancy should be considered in the differential diagnosis of infantile nystagmus.

Tear production and corneal sensitivity in diabetes.

AIM: Diabetic patients are at significant risk of developing corneal lesions such as superficial punctate keratitis, recurrent corneal erosions, persistent epithelial defects, and microbial keratitis. The aim of this study was to investigate whether diabetes mellitus is correlated with both reduced corneal sensation and reduced tear production. METHODS: In 25 type II diabetic patients with a history of retinopathy only and in 25 nondiabetic control subjects (age and sex matched), we performed noncontact corneal aesthesiometry and assessed basal tear production using Schirmer's test with topical anesthesia. The noncontact corneal aesthesiometer (NCCA) is a new noninvasive device for quantifying threshold corneal sensitivity. RESULTS: The diabetic patients demonstrated a significantly reduced Schirmer's test result (P<.001) and significantly reduced corneal sensitivity (P<.01). CONCLUSION: Our study supports previous reports of reduced basal tear production, lending more support to the theory of a peripheral neuropathy affecting lacrimal gland function in diabetes. We also confirmed reduced threshold corneal sensitivity in diabetic patients using the NCCA.

Amniotic membrane grafting for conjunctival and lid surface disease in the acute phase of toxic epidermal necrolysis.

Toxic epidermal necrolysis (TEN) is a severe form of Stevens-Johnson syndrome, characterized by extensive sloughing of mucous membranes and skin. It is associated with mortality rates of up to 70% and significant ocular morbidity in long-term survivors. We present a case of TEN with severe bilateral ocular involvement in whom we successfully used amniotic membrane grafts to treat the ocular surface during the acute phase of the disease.