Herpes Zoster Ophthalmicus Uveitis: Onset and Complications.

PURPOSE: To describe the timing of uveitis onset and frequency of associated complications in individuals with herpes zoster ophthalmicus (HZO). DESIGN: Retrospective, cohort study. METHODS: Individuals with acute HZO seen at the Auckland District Health Board from 2006 to 2016 were studied. The primary outcome measures were the proportion who developed uveitis and time to diagnosis of uveitis following the onset of HZO. Secondary outcome measures included complications of HZO uveitis and effects of prompt antiviral (within 72 hours) on outcomes. RESULTS: A total of 869 patients with HZO were included for analysis, of whom 413 (47.6%) developed uveitis. Median time from onset of rash to diagnosis of uveitis was 10 days (IQR 6-14). Of the 658 individuals examined within the first week following rash onset (days 0 through 7), 17.6% (116/658) were diagnosed with uveitis at that initial presenting examination, with an additional 24.9% (164/658) diagnosed with uveitis at a subsequent visit. Complications were higher in eyes with uveitis, including moderate or severe vision loss, corneal scarring, neurotrophic keratitis, band keratopathy, corneal melt, elevated intraocular pressure, glaucoma, and cataract (all P < .01). Prompt antiviral was associated with a lower rate of moderate vision loss among eyes with uveitis (P = .02). CONCLUSIONS: Uveitis occurred in approximately half of individuals with HZO and was most frequently diagnosed during the second week following rash onset. Eyes with uveitis were more likely to have other ocular complications and loss of vision.

Impact of microorganism virulence on endophthalmitis outcomes.

AIMS: To determine the impact of microorganism virulence on visual outcomes in endophthalmitis. METHODS: Retrospective, multicentre cohort study of patients presenting with endophthalmitis between 2006 and 2021. A literature review was conducted to divide cultured microorganisms into low and high virulence subcategories. RESULTS: 610 eyes with endophthalmitis were recruited from New Zealand, the UK and Israel. The median age was 69.4 years. The median visual acuity was hand movements at presentation and 20/120 at the final follow-up. Severe visual loss (≤20/200) occurred in 237 eyes (38.9%) at the final follow-up. The culture-positive rate was 48.5% (296 eyes). Highly virulent microorganisms were associated with a 4.48 OR of severe visual loss at the final follow-up (p<0.001) and a 1.90 OR of developing retinal detachment or requiring enucleation or evisceration during the follow-up period (p=0.028). Oral flora were observed in 76 eyes (25.7%), and highly virulent microorganisms were observed in 68 eyes (22.9%). Highly virulent microorganisms were more likely to be found after glaucoma surgery (15 eyes, 34.9%) and vitrectomy (five eyes, 35.7%) compared with intravitreal injections (two eyes, 2.9%) and cataract surgery (22 eyes, 24.2%). On multivariate analysis, the following were associated with poorer visual outcomes: poor presenting vision (p<0.001), glaucoma surgery (p=0.050), trauma (p<0.001), oral microorganism (p=0.001) and highly virulent microorganism (p<0.001). CONCLUSION: This is the first classification of microorganisms into high and low virulence subcategories that demonstrate highly virulent microorganisms were associated with poor visual outcomes and increased likelihood of retinal detachment and enucleation.

Provision of care for diabetic retinopathy in New Zealand: are there ethnic disparities?

AIMS: Ethnic disparities have been observed in treatment at first specialist appointments across various specialties within New Zealand. This study aimed to examine documentation and treatment decisions for diabetic retinopathy by ethnicity. METHODS: Retrospective audit of first specialist diabetic retinopathy clinic appointments for 388 patients at the Department of Ophthalmology, Te Whatu Ora Te Toka Tumai Auckland. Multiple domains of care were assessed, including comprehensiveness of history taking, examination, investigations and treatment decisions. RESULTS: Europeans comprised 42%, Maori only 9.5%, Pacific peoples 13.19%, Asian 32.7% and Middle Eastern/Latin American/African in 2%. Maori patients were eligible for a significantly greater number of treatments (p=0.001). The comprehensiveness of history taking (p=0.809), examination (p=0.513), investigations (p=0.623) and proportion of eligible treatments provided (p=0.788) was similar but did not reach the gold standard of care across all ethnicities. CONCLUSIONS: The standard of care provided in first specialist appointments for diabetic retinopathy appear to be similar across all ethnic groups, although Maori were underrepresented and had a higher disease burden at presentation. Our data highlights the need to reduce barriers faced by Maori in accessing GP, optometry and retinopathy screening referrals in Auckland, and improving local consultation and treatment guidelines.

Visual outcomes and prognostic factors in ischaemic retinal vasculitis.

PURPOSE: Our aim was to describe the visual outcomes and determine the clinical factors in ischaemic retinal vasculitis (IRV) that were predictive of a poor visual prognosis or infectious aetiology. METHODS: Retrospective cohort study of consecutive presentations of IRV to Auckland District Health Board from 2009 to 2022. RESULTS: The median age at presentation was 39.2 years and 108 (53.7%) were women. The total median follow-up was 4.8 years. Infectious aetiology was present in 151 eyes (52.1%). Moderate visual loss (20/50 to 20/200) occurred in 20 eyes (6.9%) and severe visual loss (≤20/200) occurred in 41 eyes (14.1%). Median visual acuity was 20/30 (IQR 20/25 to 20/100) on presentation and 20/25 (IQR 20/20 to 20/50) at final follow-up. Retinitis (HR 4.675 p=0.048) and cystoid macular oedema (CME) (HR 7.265 p<0.001) were significantly associated with vision loss. There was concurrent macular ischaemia in 26 eyes (19.4%) and CME in 52 eyes (17.9%). Retinitis was predictive of infectious aetiology (p=0.006) and cotton wool spots for non-infectious aetiology (p<0.001). Retinal haemorrhage (HR 5.580 p=0.001), retinal vein occlusion (HR 5.071 p=0.001) and quadrants of ischaemia (HR 2.222 p=0.025) were significantly associated with vitreous haemorrhage. CONCLUSION: In patients with IRV, 21% of affected individuals sustained moderate-to-severe vision loss over 5 years. Ultra-widefield fluorescein angiography can be used to quantify the risk of neovascular complications and guide treatment.

Risk of Recurrence in Acute Anterior Uveitis.

PURPOSE: To examine the frequency of recurrence and identify risk factors for recurrence in patients with acute anterior uveitis (AAU). DESIGN: Retrospective cohort study from a single tertiary ophthalmic clinical center. PARTICIPANTS: All subjects with AAU identified from a database of Inflammatory Eye Disease presenting to Te Whatu Ora (Auckland, New Zealand) between 2008 and 2021. METHODS: Data were collected retrospectively from chart review and electronic patient records for all patients during the study period. Rates of recurrence were reported using the Kaplan-Meier estimator. Multivariate analysis of risk factors for recurrence was calculated using a marginal Cox regression model. MAIN OUTCOME MEASURES: The primary outcome measure was disease recurrence. Secondary outcome measure was moderate vision loss (≤20/50). RESULTS: A total of 2763 eyes of 2092 subjects with AAU were studied, with a median follow-up time of 8.9 years and a total follow-up of 19 794.9 eye-years. Recurrence occurred in the ipsilateral eye in 1258 eyes (45.5%) and in the contralateral eye in 522 eyes (27.3%). Rates of ipsilateral recurrence over 10 years were 38.1% for idiopathic disease, 43.2% for human leukocyte antigen B27 (HLA-B27)/inflammatory arthritis, and 44.9% for viral uveitis. On multivariate analysis, the following were associated with increased risk of ipsilateral recurrence: older age (P < 0.001), Maori ethnicity (P = 0.006), Asian ethnicity (P < 0.001), HLA-B27/inflammatory arthritis (P < 0.001), and viral uveitis (P = 0.018). There was no association with gender, smoking, bilateral disease, or hypertensive uveitis. Rates of contralateral eye involvement were significantly lower than ipsilateral eye recurrence. Contralateral recurrence at 10 years was 15.2% in idiopathic uveitis, 37.6% in HLA-B27/inflammatory arthritis, and 2.0% in viral uveitis. Risk factors identified for contralateral eye involvement were Maori ethnicity (P = 0.003), Pasifika (Pacific Islanders) ethnicity (P = 0.021), and HLA-B27/inflammatory arthritis (P < 0.001). Moderate vision loss (≤20/50) was present in 411 eyes (14.9%) at final follow-up and was more common if time to first recurrence was shorter (P < 0.001). CONCLUSIONS: Approximately half of patients with AAU will develop recurrence in the ipsilateral eye, and one-quarter will have recurrence in the contralateral eye. Patients with viral disease have the highest risk of ipsilateral recurrence and lowest risk of contralateral recurrence. Patients with risk factors for recurrence should be managed and counseled appropriately to minimize the risk of visual loss and complications of uveitis. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Uveitis and Scleritis as a Risk Factor for Mortality.

PURPOSE: Uveitis and scleritis may be caused by local or systemic infection, or associated with noninfectious systemic inflammatory autoimmune disease. This study explored the all-cause mortality following an individual's first presentation with uveitis/scleritis. METHODS: A cross-sectional study was conducted on all uveitis/scleritis patients diagnosed by uveitis specialists and treated in a single tertiary referral center in New Zealand between 2006 and 2020(15y). Masquerade syndromes including intraocular lymphoma were excluded. Outcome measures: demographics, etiology of uveitis/scleritis, anatomical location and all-cause mortality. RESULTS: 2723 subjects were identified. Median age of onset of uveitis/scleritis was 44.9 years (Range:1.5-99.5 years). 49.6% were female. Median follow-up from diagnosis of uveitis/scleritis was 8.0 years (IQR 4.1-11.6 years) with a total follow-up of 24 443.3 subject-years. The most frequent diagnosis was idiopathic disease (30.9%), HLA-B27-positive uveitis (20.0%), and sarcoidosis (4.7%). Infectious etiologies (24.1%) were most commonly from herpes zoster virus (9.3%) and toxoplasmosis (4.3%). The age-adjusted mortality rate was higher in subjects with idiopathic disease, sarcoidosis, Fuchs' uveitis syndrome, granulomatosis with polyangiitis/ANCA-associated vasculitis, toxoplasmosis, and herpes zoster virus, when compared to HLA-B27-positive uveitis. Hazard of mortality peaked in the first seven years following diagnosis, then subsequently declined. Patients with uveitis/scleritis had a significantly higher rate of mortality compared to the general New Zealand population (IRR 1.656 p = 0.017). CONCLUSION: Infectious etiologies of uveitis/scleritis in this cohort were high when compared to other developed nations, attributable to data from a tertiary referral center treating inpatients. Potential shared inflammatory mechanisms in the eye and other organs can lead to concurrent non-ocular disease requiring systemic treatment, impacting an individual's longevity.

Ocular manifestations of COVID-19.

There is an increasing body of knowledge regarding how COVID-19 may be associated with ocular disease of varying severity and duration. This article discusses the literature on the ocular manifestations associated with COVID-19, including appraisal of the current evidence, suggested mechanisms of action, associated comorbidities and risk factors, timing from initial infection to diagnosis and clinical red flags. The current literature primarily comprises case reports and case series which inevitably lack control groups and evidence to support causality. However, these early data have prompted the development of larger population-based and laboratory studies that are emerging. As new data become available, a better appraisal of the true effects of COVID-19 on the eye will be possible. While the COVID-19 pandemic was officially declared no longer a "global health emergency" by the World Health Organization (WHO) in May 2023, case numbers continue to rise. Reinfection with different variants is predicted to lead to a growing cumulative burden of disease, particularly as more chronic, multi-organ sequelae become apparent with potentially significant ocular implications. COVID-19 ocular manifestations are postulated to be due to three main mechanisms: firstly, there is a dysregulated immune response to the initial infection linked to inflammatory eye disease; secondly, patients with COVID-19 have a greater tendency towards a hypercoagulable state, leading to prothrombotic events; thirdly, patients with severe COVID-19 requiring hospitalisation and are immunosuppressed due to administered corticosteroids or comorbidities such as diabetes mellitus are at an increased risk of secondary infections, including endophthalmitis and rhino-orbital-mucormycosis. Reported ophthalmic associations with COVID-19, therefore, include a range of conditions such as conjunctivitis, scleritis, uveitis, endogenous endophthalmitis, corneal graft rejection, retinal artery and vein occlusion, non-arteritic ischaemic optic neuropathy, glaucoma, neurological and orbital sequelae. With the need to consider telemedicine consultation in view of COVID-19's infectivity, understanding the range of ocular conditions that may present during or following infection is essential to ensure patients are appropriately triaged, with prompt in-person ocular examination for management of potentially sight-threatening and life-threatening diseases.

Trends in Corneal Donation From 2013 to 2022 in Aotearoa-New Zealand: Impact of Donor Age, Gender, Ethnicity, and COVID-19.

PURPOSE: To evaluate corneal donation demographics in New Zealand (NZ) and explore changes over time. METHODS: Data were collected from all donated corneas processed by the New Zealand National Eye Bank over a 10-year period from January 2013 until December 2022. Demographic data including age, self-identified ethnicity, and gender were collected, along with location and cause of death. National death data for the corresponding period were collected online from Statistics New Zealand. RESULTS: A total of 1842 donors were processed; 1414 (76.8%) were sourced from Aotearoa-New Zealand and the remainder from Australia/United States. There was a small but statistically significant median age difference between NZ donors (68 years, interquartile range 55-76) and overseas donors [66 years (interquartile range) 51-70]. Most (n = 1151 81.4%) of NZ donors died in hospital settings, with the most common cause of death being cerebrovascular (n = 444 31.4%). Individuals were less likely to donate their cornea if they were female, [incidence rate ratio (IRR) 0.746, P < 0.001] older age (IRR 0.968, P < 0.001), or if they were of Maori (IRR 0.178, P < 0.001) or Pasifika ethnicity (IRR 0.125, P < 0.001). There was also a statistically significant decrease in donation rates over time (IRR 0.945, P < 0.001). CONCLUSIONS: There remains a profound gap between the demand for corneal transplantation and corneal tissue donation, which is worsening with time. Donor age, gender, and ethnicity seem to influence corneal donation rates. These demographic differences may be ameliorated by increased education, cultural safety, further research into those willing to donate, and the establishment of an organ/tissue donation registry.

Herpes Zoster Ophthalmicus Recurrence: Risk Factors and Long-Term Clinical Outcomes.

PURPOSE: To examine the frequency of recurrences, risk factors, and long-term clinical outcomes in subjects with herpes zoster ophthalmicus (HZO). DESIGN: Retrospective cohort study. METHODS: All subjects with acute HZO seen at a single center from 2006 to 2016 were included in the study. The primary outcome measure was eye disease recurrence. The secondary outcome measure was moderate vision loss (≤20/50). RESULTS: A total of 869 patients with acute HZO were identified, with a median follow-up time of 6.3 years (interquartile range 3.7-8.9 years). In all, 551 recurrences were observed, and at least 1 recurrence was seen in 200 subjects (23.0%), with uveitis (34.8%) being the most common. The median time to first recurrence was 3.5 months. Predictors of disease recurrence included immunosuppression (P = .026), higher presenting intraocular pressure (P = .001), corneal involvement (P = .001), and uveitis (P < .001) on multivariate analysis. Topical steroids were initiated in the first month of presentation in 437 subjects, and recurrence was observed in 184 (42.1%) of these subjects. Following cessation of topical steroid treatment, recurrence occurred after a median of 1.4 months (90% within 7 months). Moderate vision loss (≤20/50) occurred in 15.5%, 28.6%, 31.4%, 50.0%, and 57.4% of eyes with 0, 1, 2, 3, and 4 or more recurrences. CONCLUSIONS: Recurrence of HZO eye disease is common, with an increased risk of vision loss with more recurrences. These findings indicate the need for close monitoring for potential recurrences, especially after cessation of topical steroid treatment, and in individuals with identified risk factors for recurrence.

Punctate Inner Choroidopathy (PIC) disease recurrence with inflammatory choroidal neovascular membrane (iCNVM) post-COVID-19 vaccine.

PURPOSE: To report a recurrence of punctate inner choroidopathy (PIC) with an inflammatory choroidal neovascular membrane (iCNVM) after the Pfizer-BioNTech COVID-19 vaccine. METHODS: Case report. RESULTS: A 38-year-old female with a history of myopia and previous episodes of PIC and iCNVM presented with distorted vision in her right eye, seven days after receiving the first dose of the Pfizer-BioNTech COVID-19 vaccine. The patient exhibited active PIC lesions with iCNVM confirmed on multimodal imaging. Treatment with a combination of oral corticosteroids and intravitreal anti-VEGF injection led to disease resolution. Subsequent COVID-19 vaccinations, administered while the patient was immunosuppressed, did not lead to disease relapse. However, relapse occurred following the fourth COVID-19 vaccine, when the patient was not immune suppressed. CONCLUSION: This case highlights the potential risk of PIC disease relapse following COVID-19 vaccination. Further research is needed to investigate the relationship between COVID-19 vaccination and PIC exacerbation, as well as to determine optimal management strategies in this population, including close observation and consideration of prophylactic immune suppression at the time of COVID-19 vaccine for high-risk individuals.

Etiology of hypopyon in patients presenting acutely to the emergency eye department and characteristics of hypopyon uveitis.

OBJECTIVE: To examine the etiology of undifferentiated hypopyon presenting acutely and to better characterize hypopyon uveitis. METHODS: Patients with hypopyon were retrospectively identified from presentations to the emergency eye department between January 2015 and 2022 and also from a uveitis database of 3,925 patients seen between January 2008 and January 2022. A total of 426 episodes of hypopyon occurred in 375 eyes in 359 patients, and medical records were reviewed for each patient. RESULTS: In all, 222 hypopyon episodes were due to uveitis, and 204 were due to nonuveitic causes. The most common cause of hypopyon was HLA-B27-associated uveitis in 146 patients (34.3%). The next most common causes were infectious keratitis in 125 patients (29.3%) and endophthalmitis in 63 patients (14.8%). Compared with those presenting with nonuveitic hypopyon, patients with uveitis tended to present younger (p < 0.001), were more likely to be male (p < 0.0001), had better initial and final visual acuities (p < 0.001), and had lower intraocular pressures (p = 0.030). CONCLUSION: About half of the cases of hypopyon were secondary to uveitis, most of them being associated with HLA-B27 conditions with a good prognosis, and the other half were secondary to infectious keratitis and endophthalmitis with a poor prognosis.

Uveitic Macular Edema: Clinical Outcomes in Real-World Practice.

PURPOSE: To examine the real-world management and outcomes of uveitic cystoid macular oedema (CME). DESIGN: Retrospective study. METHODS: Patients with uveitic CME were identified from the Inflammatory Eye Disease database. 248 eyes of 218 patients with uveitic CME were identified. Main Outcome Measures: Time to resolution, time to recurrence and vision loss. RESULTS: Median age at time of CME was 51.7 years [IQR 37.3-63.9]. Overall likelihood of resolution was 209/248 eyes (85.3%). Resolution occurred in 34.1% with topical therapy, 69.2% treated with oral prednisone (72.9% if prednisone dose ≥ 60 mg/day), 73.5% treated with orbital floor steroid, and 86.7% treated with intravitreal steroid. On multivariate analysis, ERM was associated with decreased resolution of CME (HR 0.735 p = 0.045). Additionally, infectious aetiology approached significance (HR 0.635 p = 0.059) for CME resolution. Recurrence occurred in 85 eyes (36.5%). Predictors of increased likelihood of recurrence were current smoking status (HR 1.818 p = 0.042) and subretinal fluid at diagnosis (HR 1.577 p = 0.043). Eyes with infectious aetiology had lower chance of CME resolution, but those that did resolve had lower probability of recurrence (HR 0.891 p = 0.019). Moderate vision loss (20/50-20/200) occurred in 24 eyes (9/7%) and severe vision loss (≤20/200) in 17 eyes (6.9%). CONCLUSIONS: Management of CME is challenging given the heterogeneous aetiologies, severity of the macular edema as well as response to the therapy. A high rate of resolution was observed, given sufficient time, but recurrence occurs in one-third. Current smoking status plays an important role in the risk of recurrence of CME and patients should be encouraged to stop smoking.

Management of Scleritis in Older Adults.

Scleritis, an inflammatory disease of the eye affecting scleral tissue, presents unique challenges in the older adult population. Unlike their younger counterparts, older individuals manifest a distinct spectrum of the disease with different underlying etiologies, co-morbidities, altered immune function, and an increased risk of systemic side effects from medication choices. Addressing these complexities necessitates a comprehensive and multidisciplinary approach. Treatment of choice will depend on any underlying cause but generally involves non-steroidal anti-inflammatory drugs, systemic or local corticosteroids, and potentially disease-modifying anti-rheumatic drugs. Utilization of these therapeutic agents in older adults warrants careful consideration because of their potential side-effect profiles. This article critically examines the specific concerns for the use of these drugs in older patients and reviews the existing literature on their use in this specific cohort.

Insights into the diagnosis and management of sarcoid uveitis: A review.

Sarcoidosis is a leading cause of non-infectious uveitis that commonly affects middle-aged individuals and has a female preponderance. The disease demonstrates age, sex and ethnic differences in clinical manifestations. A diagnosis of sarcoidosis is made based on a compatible clinical presentation, supporting investigations and histologic evidence of non-caseating granulomas, although biopsy is not always possible. Multimodal imaging with widefield fundus photography, optical coherence tomography and angiography can help in the diagnosis of sarcoid uveitis and in the monitoring of treatment response. Corticosteroid remains the mainstay of treatment; chronic inflammation requires steroid-sparing immunosuppression. Features on multimodal imaging such as vascular leakage may provide prognostic indicators of outcome. Female gender, prolonged and severe uveitis, and posterior involving uveitis are associated with poorer visual outcomes.

Mechanisms of blood-retinal barrier disruption related to intraocular inflammation and malignancy.

Blood-retinal barrier (BRB) disruption is a common accompaniment of intermediate, posterior and panuveitis causing leakage into the retina and macular oedema resulting in vision loss. It is much less common in anterior uveitis or in patients with intraocular lymphoma who may have marked signs of intraocular inflammation. New drugs used for chemotherapy (cytarabine, immune checkpoint inhibitors, BRAF inhibitors, EGFR inhibitors, bispecific anti-EGFR inhibitors, MET receptor inhibitors and Bruton tyrosine kinase inhibitors) can also cause different types of uveitis and BRB disruption. As malignant disease itself can cause uveitis, particularly from breast, lung and gastrointestinal tract cancers, it can be clinically difficult to sort out the cause of BRB disruption. Immunosuppression due to malignant disease and/or chemotherapy can lead to infection which can also cause BRB disruption and intraocular infection. In this paper we address the pathophysiology of BRB disruption related to intraocular inflammation and malignancy, methods for estimating the extent and effect of the disruption and examine why some types of intraocular inflammation and malignancy cause BRB disruption and others do not. Understanding this may help sort and manage these patients, as well as devise future therapeutic approaches.

Acute posterior multifocal placoid pigment epitheliopathy: clinical presentation and risk of stroke and transient ischaemic attack.

BACKGROUND/AIMS: Acute posterior multifocal placoid pigment epitheliopathy is a rare but important disease that can be associated with life-threatening complications due to cerebral vasculitis. The primary objective was to determine the incidence of neurological complications and risk factors for stroke and transient ischaemic attack (TIA) associated with acute posterior multifocal placoid pigment epitheliopathy. Secondary objectives included the clinical presentation, visual outcomes and recurrence rates. METHODS: This was a multicentre retrospective case series including 111 eyes from 60 subjects presenting from January 2009 to June 2020. RESULTS: Median age at presentation was 29 years (IQR 24.7-35.1) and 36 subjects (60.0%) were male. 20 subjects (33.3%) reported a viral prodrome. Stroke and TIA were observed in seven subjects (11.7%). Older age was the only significant risk factor for stroke/TIA (p=0.042). Vision loss occurred in seven eyes, with four eyes (3.6%) having final visual acuity 6/15-6/60 and three eyes (2.7%) having visual acuity of 6/60 or worse. Recurrence occurred in 10 subjects (16.7%). CONCLUSIONS: The presence of headache cannot reliably predict those at risk of stroke/TIA. Individuals presenting with acute posterior multifocal pigment epitheliopathy should therefore undergo a clinical neurological review and work-up for cerebral vasculitis as deemed appropriate by the treating ophthalmologist and collaborating neurologist.