Herpes zoster ophthalmicus (HZO) 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 centre 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). 551 recurrences were observed, and at least one recurrence was seen in 200 subjects (23.0%), with uveitis (34.8%) being most common. The median time to first recurrence was 3.5 months. Predictors of disease recurrence included immunosuppression (p=0.026), higher presenting intraocular pressure (p=0.001), corneal involvement (p=0.001), and uveitis (p<0.001) on multivariate analysis. Topical steroids were initiated in the first month of presentation for 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 zero, one, two, three, and four 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 those with identified risk factors for recurrence.

Neuro-ophthalmic complications of modern anti-cancer drugs.

PURPOSE: Targeted cancer therapies have been responsible for a dramatic shift in treatment strategies for cancer, and the number of drugs, classes, and indications are continually growing. Neuro-ophthalmic complications of these medications are an uncommon but important subset of adverse events which profoundly impact vision. This review aims to collate studies and reports of known neuro-ophthalmic complications of targeted therapies and describe their management. METHODS: The anti-cancer drugs included in the review were any drugs targeting specific molecules involved in the cancer disease process. PubMed, EMBASE, and Web of Science were searched using the generic names of each drug and keywords of neuro-ophthalmic conditions. The prescribing information published by the US Food and Drug Administration (FDA) for each drug was also reviewed. RESULTS: Several classes of targeted anti-cancer drugs were found to cause neuro-ophthalmic adverse effects. Immune checkpoint inhibitors are responsible for a raft of immune-related adverse events such as optic neuritis, ischemic optic neuropathy, PRES, and myasthenia gravis. Therapies with anti-VEGF activity can provoke posterior reversible leukoencephalopathy, which commonly presents with visual loss and can be fatal if not treated promptly. Inhibitors of BCR-ABL1, VEGF, ALK, and proteasomes have all been linked to optic nerve disorders which can have debilitating consequences for vision. CONCLUSION: The neuro-ophthalmic complications of modern anti-cancer drugs can limit or necessitate the withdrawal of these life-prolonging medications. Ophthalmologists should be alert for neuro-ophthalmic complications in these medications to facilitate prompt diagnosis and treatment and reduce the risk of severe and permanent consequences.

A review of neuro-ophthalmic sequelae following COVID-19 infection and vaccination.

Background: It has become increasingly clear that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect most organs in the human body, including the neurologic and ophthalmic systems. Vaccination campaigns have been developed at rapid pace around the world to protect the population from the fast-mutating virus. This review seeks to summarise current knowledge of the neuro-ophthalmic manifestations of both COVID-19 infection and vaccination. Evidence acquisition: Electronic searches for published literature were conducted using EMBASE and MEDLINE on the 30th of July 2023. The search strategy comprised of controlled vocabulary and free-text synonyms for the following terms in various combinations: "coronavirus, COVID-19, SARS-CoV-2, 2019-nCoV, vaccination, vaccine, immunisation and neuro-ophthalmology". No time range limits were set for the literature search. Published English abstracts for articles written in a different language were screened if available. Results: A total of 54 case reports and case series were selected for use in the final report. 34 articles documenting neuro-ophthalmic manifestations following COVID-19 infection and 20 articles with neuro-ophthalmic complications following COVID-19 vaccination were included, comprising of 79 patients in total. The most commonly occurring condition was optic neuritis, with 25 cases following COVID-19 infection and 27 cases following vaccination against COVID-19. Conclusions: The various COVID-19 vaccines that are currently available are part of the global effort to protect the most vulnerable of the human population. The incidence of neuro-ophthalmic consequences following infection with COVID-19 is hundred-folds higher and associated with more harrowing systemic effects than vaccination against the virus.

Optic atrophy in prematurity: pathophysiology and clinical features.

Optic atrophy is an important cause of visual impairment in children, and the aetiological profile has changed over time. Technological advancements led by neuroimaging of the visual pathway and imaging of the optic nerve with optical coherence tomography have accelerated the understanding of this condition. In the new millennium, an increasing prevalence of prematurity as a cause of optic atrophy in children has been highlighted. This new shift has been linked with increasing rates of premature births and improved neonatal survival of preterm infants. The available literature is limited to hospital and registry-based cohorts with modest sample sizes, methodological heterogeneity and selection bias limitations. Larger studies that are better designed are required to better understand the contribution of prematurity to the disease burden. In addition to considering other life-threatening aetiologies, screening for premature birth should be covered as part of a comprehensive history when evaluating a child with paediatric optic atrophy.

Patient factors associated with appointment non-attendance at an ophthalmology department in Aotearoa New Zealand.

AIM: Appointment non-attendance is a problem for medical outpatient clinics, which can result in interruption of continuity of care and poor health outcomes for patients. Furthermore, non-attendance creates a significant economic burden to the health sector. This study aimed to identify factors that are associated with appointment non-attendance in a large public ophthalmology clinic in Aotearoa New Zealand. METHODS: This study was a retrospective analysis of clinic non-attendance within Auckland District Health Board's (DHB) Ophthalmology Department between 1 January 2018 to 31 December 2019. Demographic data collected included: age, gender and ethnicity. Deprivation Index was calculated. Appointments were classified as new patients and follow-ups, and acute or routine. Categorical and continuous variables were analysed using logistic regression to assess likelihood of non-attendance. The research team's expertise and capacity align with the CONSIDER statement guidelines for Indigenous health and research. RESULTS: In total, 52,512 patients were scheduled to attend 227,028 outpatient visits, of which 20,580 visits (9.1%) were not attended. Median age of patients who received one or more scheduled appointments were 66.1 years (interquartile range [IQR] 46.9-77.9). Fifty-one point seven percent of patients were female. Ethnicity comprised 55.0% European, 7.9% Maori, 13.5% Pacific peoples, 20.6% Asian and 3.1% Other. Multivariate logistic regression analysis for all appointments showed that males (odds ratio [OR] 1.15 p<0.001), younger patients (OR 0.99 p<0.001), Maori (OR 2.69 p<0.001), Pacific peoples (OR 2.82 p<0.001), higher deprivation status (OR 1.06 p<0.001), new patient appointments (OR 1.61 p<0.001) and patients referred to acute clinics (OR 1.22 p<0.001) were more likely to not attend appointments. CONCLUSIONS: Maori and Pacific peoples disproportionately experience higher rates of appointment non-attendance. Further investigation of access barriers will enable Aotearoa New Zealand health strategy planning to develop targeted interventions addressing unmet patient needs of at-risk groups.

Current practice of trabeculectomy in a cohort of experienced glaucoma surgeons in Australia and New Zealand.

BACKGROUND/OBJECTIVES: To evaluate current routine trabeculectomy technique preferences among Australian and New Zealand Glaucoma Society surgeons regularly performing trabeculectomy surgery. SUBJECTS/METHODS: Survey of experienced surgeons who perform trabeculectomy. RESULTS: Forty-nine surgeons (33 male:16 female) participated in the survey. Trabeculectomy was performed as day surgery (39/47, 83.0%) under local anesthesia (44/47, 93.6%). The surgical techniques most commonly used were a corneal traction suture (44/47, 93.6%), fornix-based conjunctival flap (43/47, 91.5%) and half-thickness scleral flap (38/47, 81.0%). Mitomycin C antifibrotic agent was used in routine cases by 45/46 (97.8%) surgeons. Surgeons applied the antifibrotic agent under the Tenon layer with a pledget (36/46, 78.2%) with a concentration of 0.02% (37/46, 80.4%) for 2 (11/46, 23.9%) or 3 min (30/46, 65.2%). The Kelly (26/46, 56.5%) and the Khaw Descemet (19/46, 41.3%) punches were used to perform the sclerostomy. Most surgeons performed a peripheral iridectomy in all phakic patients (46/47, 97.9%), but less commonly in pseudophakic patients (34/47, 72.3%). Techniques for closure of the limbal conjunctival edge were quite varied with a combination of suturing including purse string (21/47, 57.4%), wing (20/47, 42.6%) and horizontal mattress sutures (33/47, 70.2%). Surgeons reviewed their routine patients four times in the first month (29/47, 61.7%) and continued the postoperative topical steroids for 3-4 months (28/47, 59.6%). CONCLUSIONS: Although a wide range of techniques for trabeculectomy exists among surgeons, there are consistent procedures currently in use to optimize patient outcomes. This report will assist surgeons in choosing which surgical techniques fit their best practice.

Nonarteritic Anterior Ischemic Optic Neuropathy After Cataract Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: Nonarteritic anterior ischemic optic neuropathy (NAION) has been reported to occur after cataract surgery. It is not clearly established whether cataract surgery increases the risk of NAION over baseline. EVIDENCE ACQUISITION: Medline, PubMed, Embase, and Cochrane Central registers were systematically searched for eligible studies reporting on postcataract surgery NAION (psNAION) within 1 year. All peer-reviewed publications with events n ≥ 10 were included. Pooled incidence and odds/hazard ratios and 95% confidence intervals (CIs) were extracted and calculated using random effect models for early and delayed psNAION. Time to event data were pooled for temporal analysis of psNAION events within the first year. This systematic review was registered (PROSPERO CRD42021274383). RESULTS: Nine articles met the selection criteria with five studies suitable for meta-analysis. A total of 320 psNAION cases, 1,307 spontaneous NAION (sNAION) cases, 1,587,691 cataract surgeries, and 1,538,897 noncataract surgery controls were included. Pooling of 63,823 cataract surgeries and 161,643 controls showed a hazard ratio of 4.6 (95% CI 2.7-7.8) of psNAION within 1 year of surgery. Pooled unadjusted incidence of psNAION within 2 months was 99.92 (95% CI 38.64-161.19) per 100,000/year, psNAION within 1 year was 32.36 (95% CI 9.38-55.34) per 100,000/year, and sNAION was 8.87 (95% CI 2.12-15.62) per 100,000/year. psNAION cases were older by a mean of 7.6 years; otherwise, pooled odds ratios for baseline risk factors in psNAION vs. sNAION cases were not statistically significant. psNAION within the first year peaked within 72 hrs and at 6 weeks after the surgery with 73% of cases occurring within 6 months. CONCLUSION: The risk of NAION after cataract surgery is four times greater within the first year and usually occurs within 6 months. However, the absolute risk remains low at 1 in 1,000-3,100 surgeries and is unlikely to warrant extra mention for consenting.

Eye Movements in Mild Traumatic Brain Injury: Clinical Challenges.

Mild traumatic brain injury (mTBI), also known as concussion, is a common injury which affects patients of all demographics. There is a global effort to accurately diagnose and identify patients at highest risk of prolonged symptom burden to facilitate appropriate rehabilitation efforts. Underreporting is common with large numbers not engaging with services, in addition to differences in treatment outcomes according to ethnicity, age, and gender. As patients recover, symptomology evolves which challenges rehabilitative efforts with no clear definition of 'recovered'. This review describes key areas in mTBI such as diagnostic challenges, epidemiology, prognosis, and pathophysiology which serves as an introduction to "Eye Movements in Mild Traumatic Brain Injury: Ocular Biomarkers."

Eye Movements in Mild Traumatic Brain Injury: Ocular Biomarkers.

Mild traumatic brain injury (mTBI, or concussion), results from direct and indirect trauma to the head (i.e. a closed injury of transmitted forces), with or without loss of consciousness. The current method of diagnosis is largely based on symptom assessment and clinical history. There is an urgent need to identify an objective biomarker which can not only detect injury, but inform prognosis and recovery. Ocular motor impairment is argued to be ubiquitous across mTBI subtypes and may serve as a valuable clinical biomarker with the recent advent of more affordable and portable eye tracking technology. Many groups have positively correlated the degree of ocular motor impairment to symptom severity with a minority attempting to validate these findings with diffusion tract imaging and functional MRI. However, numerous methodological issues limit the interpretation of results, preventing any singular ocular biomarker from prevailing. This review will comprehensively describe the anatomical susceptibility, clinical measurement, and current eye tracking literature surrounding saccades, smooth pursuit, vestibulo-ocular reflex, vergence, pupillary light reflex, and accommodation in mTBI.

Eye Movement Abnormalities in Glaucoma Patients: A Review.

Glaucoma is a common condition that relies on careful clinical assessment to diagnose and determine disease progression. There is growing evidence that glaucoma is associated not only with loss of retinal ganglion cells but also with degeneration of cortical and subcortical brain structures associated with vision and eye movements. The effect of glaucoma pathophysiology on eye movements is not well understood. In this review, we examine the evidence surrounding altered eye movements in glaucoma patients compared to healthy controls, with a focus on quantitative eye tracking studies measuring saccades, fixation, and optokinetic nystagmus in a range of visual tasks. The evidence suggests that glaucoma patients have alterations in several eye movement domains. Patients exhibit longer saccade latencies, which worsen with increasing glaucoma severity. Other saccadic abnormalities include lower saccade amplitude and velocity, and difficulty inhibiting reflexive saccades. Fixation is pathologically altered in glaucoma with reduced stability. Optokinetic nystagmus measures have also been shown to be abnormal. Complex visual tasks (eg reading, driving, and navigating obstacles), integrate these eye movements and result in behavioral adaptations. The review concludes with a summary of the evidence and recommendations for future research in this emerging field.

Imaging of the optic nerve: technological advances and future prospects.

Over the past decade, ocular imaging strategies have greatly advanced the diagnosis and follow-up of patients with optic neuropathies. Developments in optic nerve imaging have specifically improved the care of patients with papilloedema and idiopathic intracranial hypertension, inflammatory optic neuropathies, and compressive optic neuropathies. For example, optic nerve imaging with optical coherence tomography (OCT) is now widely used as an outcome measure in clinical trials of neurological disorders (eg, demyelinating diseases), and OCT findings could be informative of disease progression in patients with various neurodegenerative disorders (eg, Alzheimer's disease or Parkinson's disease). In the past 5 years, multimodality optic nerve imaging has expanded to systematically include focused and wide-field colour and autofluorescence fundus photographs; various types of optic nerve, macular, and vascular OCT; and specific MRI techniques. Such multimodality imaging makes the diagnosis of optic neuropathies easier and provides objective information on optic nerve damage, which is useful for prognosis. Non-mydriatic ocular fundus cameras and OCT have become readily available in non-ophthalmic settings and could easily be implemented in neurological clinics and emergency departments, allowing for direct access to optic nerve imaging and enabling teleconsultations. In the future, these imaging studies could be used in association with artificial intelligence deep-learning systems, which are already transforming the field of ocular imaging.

A window into eye movement dysfunction following mTBI: A scoping review of magnetic resonance imaging and eye tracking findings.

Mild traumatic brain injury (mTBI), commonly known as concussion, is a complex neurobehavioral phenomenon affecting six in 1000 people globally each year. Symptoms last between days and years as microstructural damage to axons and neurometabolic changes result in brain network disruption. There is no clinically available objective biomarker to diagnose the severity of injury or monitor recovery. However, emerging evidence suggests eye movement dysfunction (e.g., saccades and smooth pursuits) in patients with mTBI. Patients with a higher symptom burden and prolonged recovery time following injury may show higher degrees of eye movement dysfunction. Likewise, recent advances in magnetic resonance imaging (MRI) have revealed both white matter tract damage and functional network alterations in mTBI patients, which involve areas responsible for the ocular motor control. This scoping review is presented in three sections: Section 1 explores the anatomical control of eye movements to aid the reader with interpreting the discussion in subsequent sections. Section 2 examines the relationship between abnormal MRI findings and eye tracking after mTBI based on the available evidence. Finally, Section 3 communicates gaps in our knowledge about MRI and eye tracking, which should be addressed in order to substantiate this emerging field.

Prompt Antiviral Therapy Is Associated With Lower Risk of Cerebrovascular Accident Following Herpes Zoster Ophthalmicus.

PURPOSE: To examine risk factors associated with cerebrovascular accident (CVA) following herpes zoster ophthalmicus (HZO). DESIGN: Retrospective cohort study. METHODS: Review of medical records of all patients with HZO seen at the department of Ophthalmology, Auckland District Health Board, New Zealand, between January 1, 2006, and December 31, 2016. The main outcome measure was cerebrovascular accident within 12 months of diagnosis. RESULTS: A total of 869 patients diagnosed with HZO were included in the study. The median age at onset of HZO was 65.5 years (interquartile range [IQR] 52.9-75.4), and 52.5% (n=456) were male. Antiviral therapy was started in 765 participants (88.0%), not used in 95 (10.9%), and not documented in 9 participants (1.0%). Four hundred sixty-eight participants (54.9%) received prompt oral antiviral therapy (≤72 hours of rash onset). A CVA occurred in the 12 months following HZO in 14 patients (1.6%) and was most common in older patients, occurring in 2.5% aged ≥65 years, 0.7% aged 40-65 years, and 0.9% aged <40 years. Hazard of CVA was highest immediately following HZO, with median time to CVA of 2.3 months (IQR 0.8-5.9 months). Patients who received prompt acyclovir had a 76.2% lower hazard of CVA (0.9% vs 2.6%, P = .022) on multivariate analysis. CONCLUSIONS: Cerebrovascular accident occurs in a low proportion of individuals within 1 year following HZO. Antiviral treatment for HZO may reduce the risk of subsequent CVA when given within 72 hours of rash onset.

Deadbolt cataract due to misplanted minishunt.

A 62-year-old woman with stable unilateral glaucoma in the left eye presented for a cataract consultation. In 2010, laser peripheral iridotomies (LPI) were performed on both eyes by a different provider. Her postoperative course was complicated by a recalcitrant steroid response with a highest intraocular pressure (IOP) of 65 mm Hg in the left eye. A trabeculectomy with a glaucoma minishunt (EX-PRESS, Alcon) was then performed by that provider (Supplemental Figure 1, http://links.lww.com/JRS/A603). Thereafter, IOP control of the left eye was normalized and maintained without topical antiglaucoma medications. Historically, her right eye has been always her better eye. Recently, she noticed metamorphopsia in her left eye. Her ocular history was also notable for high refractive errors requiring continuous spectacles wear, possible mild refractive amblyopia of the left eye, history of submacular choroidal nevus with drusen in the right eye, and an epiretinal membrane (ERM) with macular pucker in the left eye. Her husband is an optician. Both inquire about refractive cataract surgery options to correct astigmatism and presbyopia; both have reservations regarding cost and visual quality associated with diffractive optic intraocular lenses (IOLs). Her deteriorating visual acuity in both eyes affects her ability to work. Her corrected distance visual acuity was 20/40 in both eyes (pinhole, no help) while wearing spectacles according to a prescription of -8.50 diopters (D) +1.50 D × 106 for the right eye and -13.00 D +3.25 D × 057 for the left eye. Her corrected near visual acuity was 14/14 in both eyes with the abovementioned prescription and a +3.00 D add. Central corneal thickness was 618 µm in the right eye and 631 µm in the left eye. IOP was 20 mm Hg in the right eye and 10 mm Hg in the left eye on no antiglaucoma medications. Pertinent findings on slitlamp examination included bilateral dermatochalasis, a shallow diffuse thick bleb superiorly in the left eye only, patent LPI superiorly in both eyes, nuclear sclerotic and cortical cataracts in both eyes (with prominent focal spoke superiorly left eye only) (Figure 1, A-C). Fundus photos show posterior vitreous detachment in both eyes, ERM with macular pucker in the left eye, and submacular choroidal nevus (2.5 × 3.0 disc diameter size) with overlying drusen in the right eye (Supplemental Figure 2, A, http://links.lww.com/JRS/A604). Gonioscopy revealed open angles in both eyes, albeit with focal narrowing without synechiae superiorly in the left eye only (Figure 1, D-FJOURNAL/jcrs/04.03/02158034-202207000-00020/figure1/v/2022-06-24T130746Z/r/image-tiff). Most importantly, however, the distal tip of the minishunt was not positioned as expected in the anterior chamber; rather, it was noted to pierce the peripheral iris near the iris root superiorly. Most of the minishunt shaft and spur were positioned in the posterior chamber with the distal tip penetrating into the superior aspect of the capsular bag and cataract in the left eye-like a deadbolt. Visual field testing showed a full field in the right eye and an inferior nasal step in the left eye (Supplemental Figure 2, B, http://links.lww.com/JRS/A604). In addition to slitlamp, gonioscopic, and fundus photos, we also obtained optical coherence tomography of the macula and nerve (Supplemental Figure 2, C, http://links.lww.com/JRS/A604), optical biometry, ultrasound biomicroscopy, endothelial cell counts, and corneal topography (Supplemental Figure 3, http://links.lww.com/JRS/A605). How would you counsel this patient regarding her glaucoma condition, the misplanted minishunt, and her cataract surgery and IOL options? How would you manage the misplanted minishunt? What surgical approaches or specific techniques would you consider for cataract removal and visual rehabilitation?

COVID-19 Vaccination and The Eye.

PURPOSE: To summarize the current evidence on COVID-19 vaccine-associated ocular adverse events. DESIGN: Narrative literature review. METHODS: The literature search was conducted in August 2021 using 4 electronic databases: MEDLINE, EMBASE, PubMed, and the Cochrane Database of Systematic Reviews. Population-based pharmacovigilance surveillance data were retrieved from all governmental agencies participating in the World Health Organization (WHO) Programme for International Drug Monitoring with publicly available online adverse event databases in English. RESULTS: A small number of case reports have documented uveitis flares and acute corneal graft rejection occurring within the first 3 weeks following immunization, while isolated cases of optic neuropathies, retinal conditions, scleritis, and herpetic eye disease have also been highlighted. However, data from population-based pharmacovigilance surveillance systems suggest that the prevalence of vaccination-associated ocular adverse events are very rare. CONCLUSIONS: Vaccination-associated ocular adverse events are rare, and there is currently no substantive evidence to counterweigh the overwhelming benefits of COVID-19 immunization in patients with pre-existing ophthalmic conditions.

Neurotrophic Keratopathy After Herpes Zoster Ophthalmicus.

PURPOSE: The aim of this study was to describe risk factors for neurotrophic keratopathy (NK) after herpes zoster ophthalmicus (HZO). METHODS: This study was a retrospective review of all patients seen at the Auckland District Health Board with HZO from 2006 through 2016. Cox proportional hazards analysis was performed to examine time to development of neurotrophic keratitis. RESULTS: Eight hundred sixty-nine patients were included in the study with a median follow-up of 6.3 years (5504.4 patient-years). The median age was 65.5 years (interquartile range 52.9-75.4), and 456 subjects (52.5%) were male. NK developed in 58 patients (6.7%), with the highest hazard 1 to 2 years after onset of HZO. On univariate analysis, age, White ethnicity, best-corrected visual acuity (BCVA) at presentation, intraocular pressure, corneal involvement, uveitis, and number of recurrences were associated with increased risk of NK. On multivariate analysis, the following factors were significant: age (hazard ratio [HR] = 1.03; P = 0.021), White ethnicity (HR = 3.18; P = 0.015), BCVA (HR = 1.81; P = 0.026), uveitis (HR = 3.77; P = 0.001), and recurrence (HR = 1.34; P < 0.001). Vision loss (BCVA ≤6/15) was more frequent in subjects with NK (65.5% vs. 16.3%, P < 0.001). CONCLUSIONS: NK is a relatively common and serious complication of HZO and occurs more frequently in older White individuals, those with poor visual acuity at presentation, and those with uveitis. Vision loss occurs in approximately two-thirds of patients.

Stroke risk after ocular cranial nerve palsy - A systematic review and meta-analysis.

BACKGROUND: Isolated ischemic ocular cranial nerve palsies (OCNP) involving the 3rd, 4th and 6th cranial nerves (CN) are prevalent conditions in ophthalmic practice. However, it is not clearly established whether such patients are at increased risk of stroke after onset of OCNPs. METHODS: Medline, PubMed, Embase and Cochrane Central registers were systematically searched for eligible studies comparing isolated ischemic OCNPs against matched controls on the subsequent development of stroke with at least two years of follow up. Case reports and series were excluded. Appropriate studies were entered for meta-analysis to determine hazard ratios. Search and data extraction was completed on 22 Feb 2021. Random effect models were used to generate pooled hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Three studies were suitable for meta-analysis (total n = 2,756 OCNP cases and 21,239 matched controls). The meta-analysis demonstrated a hazard ratio of 5.96 (4.20-8.46 95% CI) of subsequent stroke after isolated OCNP within the first year. The hazard ratio reduced to 3.27 (2.61-4.10 95% CI) after five years although remains raised at 2.49 (1.53-4.06 95% CI) up to 12 years. The highest risk was demonstrated with 3rd cranial nerve palsies. Two additional studies assessed the risk of stroke with newly diagnosed diabetics and compared OCNPs against lacunar stroke. These studies did not demonstrate a significant increased risk of stroke, although they may be statistically underpowered. CONCLUSION: Ischemic OCNPs represent a significant risk factor for development of subsequent stroke in a similar magnitude to transient ischemic attack within the first year.