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.

Optic neuropathy from hypovitaminosis A in a series of children with severe dietary restrictions.

AIM: Hypovitaminosis A is a leading cause of preventable childhood blindness, especially in developing nations. Vitamin A is a fat-soluble essential micronutrient that serves vital functions in the visual system and in regulating bone resorption. We report on a series of four children with mixed nutritional and compressive optic neuropathy and provide a review of the literature. METHODS: A retrospective observational study of four males (ages 9-12), three with autism spectrum disorder who presented with loss of vision and multiple vitamin deficiencies including hypovitaminosis A. RESULTS: Patients presented with unexplained visual loss or a change in visual behaviour. All patients had severely restricted diet comprising of predominantly carbohydrates. Two of the four cases demonstrated optic nerve pallor at initial presentation with marked optic atrophy developing in all patients over time. Electrophysiology available in two patients demonstrated optic nerve dysfunction with preserved retinal function. Extensive investigations revealed profound deficiency in multiple vitamins including vitamin A (<0.1-0.2 µmol/L, normal = 0.9-1.7 µmol/L). Three patients also had low vitamin B12 (90-111 pmol/L, normal = 170-800 pmol/L) with normal folate. All four cases had radiological evidence of skull base thickening indicative of low vitamin A. Genetic testing did not find any relevant pathogenic variants. CONCLUSIONS: Hypovitaminosis A is a crucial form of nutritional deprivation that results in significant visual loss with potential hyperostosis and optic nerve compression exacerbating nutritional optic neuropathy. Additional micronutrient deficiencies usually co-exist and may contribute. Extra vigilance in vitamin replacement is required of clinicians with patients with autism who have restricted diets.

Optic Atrophy From Retrograde Transsynaptic Axonal Degeneration Following Pediatric Brain Injury.

BACKGROUND: The patterns of optic atrophy due to retrograde transsynaptic degeneration (RTSD) have not been well characterized in children. This study aimed to characterize optic atrophy in pediatric patients with focal intracerebral lesions. METHODS: A retrospective review of children with optic atrophy and focal intracerebral lesions was conducted. Ophthalmic data were recorded, including visual acuity, color vision, formal automated visual fields and optical coherence tomography (OCT) of the peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell layer. RESULTS: Six patients (83.33% male) were included. The mean visual acuity (VA) of all eyes was 0.30 logMAR (20/40 Snellen), with no significant difference in the mean logMAR VA in the ipsilateral eye to the location of the lesion compared with the contralateral eye (0.30 vs 0.30, P = 1.000). Color vision (available in 5 patients) was normal in 2, mildly reduced in one and markedly reduced in 2. Bitemporal optic disc pallor was observed in 5 out of 6 patients. OCT data revealed that pRNFL thickness was most significantly diminished in the temporal (95% CI: -44.71 to -14.18 µm, P = 0.0021), inferotemporal (95% CI: -75.06 to -5.17 µm, P = 0.0294), and superotemporal (95% CI: -76.82 to -18.51 µm, P = 0.0055) sectors. Average pRNFL thickness was significantly reduced compared with normative data in both the ipsilateral (95% CI: -40.76 to -11.69 µm, P = 0.0003) and the contralateral eye (95% CI: -38.46 to -5.83 µm, P = 0.0063). When only nasal and temporal data were analyzed, mean pRNFL thickness was still diminished compared with normative data (95% CI: -33.01 to -9.77 µm, P = 0.0012). CONCLUSIONS: Children presenting with optic atrophy, particularly with bitemporal optic atrophy, should have neuroimaging to exclude any underlying serious intracranial pathology.

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.

Tonabersat Significantly Reduces Disease Progression in an Experimental Mouse Model of Multiple Sclerosis.

Multiple sclerosis (MS) is a neurodegenerative disease marked by chronic neuroinflammation thought to be mediated by the inflammasome pathway. Connexin 43 (Cx43) hemichannels contribute to the activation of the inflammasome through the release of adenosine triphosphate (ATP) inflammasome activation signals. The objective of the study was to evaluate if the Cx43 hemichannel blocker, tonabersat, is effective in modulating the inflammatory response and reducing disability in the myelin oligodendrocyte glycoprotein 35-55-induced experimental autoimmune encephalomyelitis (MOG35-55 EAE) model of MS. Here, we show that the Cx43 hemichannel blocking drug, tonabersat, significantly reduced expression of neuroinflammatory markers for microglial activation (ionized calcium-binding adapter molecule 1 (Iba1)) and astrogliosis (glial fibrillary acidic protein (GFAP)) while preserving myelin basic protein (MBP) expression levels in the corpus callosum, motor cortex, and striatum regions of the brain in MOG35-55 EAE mice. Reduced NOD-like receptor protein 3 (NLRP3) inflammasome complex assembly and Caspase-1 activation confirmed the drug's mode of action. MOG35-55 EAE mice showed clinical signs of MS, but MOG35-55 EAE mice treated with tonabersat retained behavior closer to normal. These data suggest that clinical trial phase IIb-ready tonabersat may merit further investigation as a promising candidate for MS treatment.

A comparison of macular ganglion cell and retinal nerve fibre layer optical coherence tomographic parameters as predictors of visual outcomes of surgery for pituitary tumours.

PURPOSE: The prognostic value of optical coherence tomography (OCT) of the macular ganglion cell layer (mGGL) versus peripapillary retinal nerve fibre layers (pRNFL) following chiasmal decompression is unclear. This study is the largest comparison of the two parameters to date and aims to clarify how their performance as covariates compare in predictive models of long-term visual outcomes following pituitary or parasellar tumour surgical resection. METHODS: This was a prospective, two-year, longitudinal cohort study in a single centre tertiary hospital setting. Participants with MRI evidence of pituitary or parasellar tumour compression of the optic chiasm who underwent surgical decompression, were enrolled. Associations between pre-operative OCT parameters and long-term visual outcomes were assessed using multivariable generalised linear mixed models and an age matched normative database. RESULTS: Final analysis included 216 eyes of 108 participants with a mean age (standard deviation) of 51.6 (17.04) years, of whom 58 (49%) were female. The superior inner mGCL was the best predictor of long-term visual field recovery, with an area under the curve of 0.90, a sensitivity of 80%, specificity of 88%, positive predictive value of 86%, and negative predictive value of 83%. CONCLUSION: mGCL performed better in predicting long-term visual field recovery post-pituitary or parasellar surgical resection. The superior inner mGCL was the best specific measure which may provide clinical utility in pre-operative counselling. In this study we clarify previously variable comparisons of mGCL and pRNFL parameters in post-operative predictive modelling.

Gender differences in surgical case volume among ophthalmology trainees.

BACKGROUND: The number of females in ophthalmology has steadily increased over recent decades. The aim of this study was to evaluate whether there is a difference in procedural volume and cataract surgery between male and female trainees in the Royal Australian and New Zealand College of Ophthalmologists (RANZCO). METHODS: A longitudinal retrospective review of de-identified surgical RANZCO trainee logbook data from 2008 to 2020 was undertaken. Data from 241 trainee logbooks were analysed for: location of training, gender, date of commencement of training, maternity/paternity leave status, number of surgeries observed, assisted, supervised and unsupervised. Surgical cases were grouped as: (1) all surgical cases; (2) complete cataract cases and (3) partial cataract cases. RESULTS: Among 241 trainees (40.7% females), 197 263 procedures were performed. Total surgical volume was 21.1% lower at 4 years for females (median 665.5 vs. 843.5; p = 0.036). Completed cataract surgery was 21.5% lower at 18 months (median 87.5 vs. 111.5; p = 0.022) and 41.7% lower at 4 years (median 216 vs. 369; p < 0.001). Interrupted training was significantly more common in females (30.6% vs. 0.7%; p < 0.001). However, linear regression analysis did not identify parental leave or duration as a significant predictor for number of completed cataracts (p = 0.206). Complication rate was not different between males and females (p = 0.35). CONCLUSIONS: Female trainees completed 41.7% fewer cataract operations at the end of their training compared to male counterparts with the gap widening between years 1 and 4 of training. The current data demonstrates that female and male RANZCO trainees are not receiving equivalent operating experiences.

Neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein IgG associated disorder: A comprehensive neuro-ophthalmic review.

Neuromyelitis optica spectrum disorder (NMOSD) is an antibody-mediated inflammatory disease of the central nervous system that involves the optic nerves, spinal cord, and often other specific brain regions such as area postrema of the medulla. NMOSD was formerly classified as a variant of multiple sclerosis (MS), given the similar symptomatology and relapsing course but is now considered to have distinct clinical, paraclinical, immunological and prognostic features. The discovery of aquaporin 4 (AQP4) immunoglobulin G (IgG) has improved the ability to diagnose NMOSD. AQP4-IgG targets the astrocytic AQP4 water channel leading to complement activation and increased blood-brain barrier permeability. Accurate and early diagnosis is crucial as timely treatment may result in mitigation of long-term disability. Myelin oligodendrocyte glycoprotein (MOG)-IgG associated disorder (MOGAD) is a distinct nosologic entity, which has been more recently described. Its clinical spectrum partly overlaps that of seronegative NMOSD and MS. Although it is considered to have fewer relapses and better prognosis than NMOSD, the clinical course and outcome of MOGAD has not been fully characterized.

Bullying, harassment and sexual discrimination among ophthalmologists in Australia and New Zealand.

BACKGROUND: Discrimination, bullying and sexual harassment (DBSH) impact the psychological well-being of doctors and contribute to poor health outcomes. The Royal Australian and New Zealand College of Ophthalmologists (RANZCO) commissioned independent surveys to evaluate DBSH among members/trainees. METHODS: Anonymous online surveys by Best Practice Australia were undertaken in 2015 and 2018. Cross-sectional analysis was prevalence of perceived DBSH, rates of reporting, intervention and resolution undertaken. Response rate was 50% (658/1319) in 2015 and 40% (557/1401) in 2018. In both surveys, 29% were female. This is representative of the distribution of the RANZCO members. RESULTS: In a 2015 survey, 37.6% of respondents experienced DBSH, with prevalence being the highest for females (62.3%; N = 104 cf males 27.7%; N = 167) and trainees (49.2%; N = 61). In 2018, 49.2% of respondents reported DBSH with rates low for all forms of DBSH (22%-29%). Sexual harassment was reported by 12% and the least discussed or reported. Respondents strategy for taking action included draw on personal support network (25-43%), official complaints to supervisors (16-22%), human resources (2%-10%) and RANZCO (0%-6%). Reasons for not taking action included fear of impact of future career options (54.1%-60.7%), fear of victimization (35.7%-50.4%) and afraid of not being believed (31.9%-52.4%). Satisfactory resolution rates were 6% to 25%. A majority of respondents (77%) were positive about RANZCO initiatives. CONCLUSIONS: DBSH is commonly reported by RANZCO members with female ophthalmologists more than two times more likely to experience any one of the four behaviours, three times more likely to experience discrimination and six times for sexual harassment. Fear of compromising personal and career progression contribute to low levels of reporting.

Microdroplet and spatter contamination during phacoemulsification cataract surgery in the era of COVID-19.

IMPORTANCE: Determine phacoemulsification cataract surgery risk in a Covid-19 era. BACKGROUND: SARS-CoV-2 (Covid-19) transmission via microdroplet and aerosol-generating procedures presents risk to medical professionals. As the most common elective surgical procedure performed globally; determining contamination risk from phacoemulsification cataract surgery may guide personal protection equipment use. DESIGN: Pilot study involving phacoemulsification cataract surgery on enucleated porcine eyes by experienced ophthalmologists in an ophthalmic operating theatre. PARTICIPANTS: Two ophthalmic surgical teams. METHODS: Standardized phacoemulsification of porcine eyes by two ophthalmologists accompanied by an assistant. Fluorescein incorporated into phacoemulsification irrigation fluid identifying microdroplets and spatter. Contamination documented using a single-lens reflex camera with a 532 nm narrow bandpass (fluorescein) filter, in-conjunction with a wide-field blue light and flat horizontal laser beam (wavelength 532 nm). Quantitative image analysis using Image-J software. MAIN OUTCOME MEASURES: Microdroplet and spatter contamination from cataract phacoemulsification. RESULTS: With phacoemulsification instruments fully within the eye, spatter contamination was limited to <10 cm. Insertion and removal of the phacoemulsification needle and bimanual irrigation/aspiration, with irrigation active generated spatter on the surgeons' gloves and gown extending to >16 cm below the neckline in surgeon 1 and > 5.5 cm below the neckline of surgeon 2. A small tear in the phacoemulsification irrigation sleeve, presented a worse-case scenario the greatest spatter. No contamination above the surgeons' neckline nor contamination of assistant occurred. CONCLUSIONS AND RELEVANCE: Cataract phacoemulsification generates microdroplets and spatter. Until further studies on SARS-CoV-2 transmission via microdroplets or aerosolisation of ocular fluid are reported, this pilot study only supports standard personal protective equipment.

Gender differences in Australasian ophthalmologists' experiences of the workplace.

IMPORTANCE: Gender differences were identified in experiences of the workplace and family responsibilities amongst Australian and New Zealand ophthalmologists. BACKGROUND: To survey ophthalmologists regarding their balance of career, family and workplace experiences and to identify gender differences. DESIGN: Online questionnaire sent to 1000 randomly selected Royal Australian and New Zealand College of Ophthalmologists (RANZCO) Fellows in 2017. PARTICIPANTS: The response rate was 28% (n = 282) with 192 males. METHODS: Confidential questionnaire. MAIN OUTCOME MEASURES: Questionnaire responses. RESULTS: Gender differences were noted in working hours (59% of males worked greater than 40 hours a week vs 26% of females, P < 0.001) and frequency of private practice work (mean of 6.6 half-day sessions per week for men vs 4.9 sessions for women, P < 0.001). Female ophthalmologists reported additional obstacles to career advancement including difficulty receiving mentorship (57% vs 40%, P = 0.027), travel difficulties due to family responsibilities (59% vs 34%, P < 0.001) and rigid timelines for promotion/tenure (38% vs 19%, P = 0.005). Female ophthalmologists delayed child-bearing, with 59% becoming parents after fellowship training. Women spent more time child-rearing (67% vs 8% of men cared for children >20 hours per week, P < 0.001). Female ophthalmologists were more likely to report experiencing discrimination (31% vs 8% of men, P < 0.001). CONCLUSIONS AND RELEVANCE: Female ophthalmologists worked fewer hours, mainly in the private sector, to fulfil their greater family commitments. Female ophthalmologists reported additional obstacles to career advancement and were more likely to report experiencing discrimination in the workplace.

Presumed autoimmune retinopathy following chickenpox; a case report.

PURPOSE: To report a case of presumed autoimmune retinopathy in a patient who had been diagnosed with chickenpox immediately prior to symptom onset. METHOD: This is a retrospective case report with fundus autofluorescence and spectral-domain optical coherence tomography. RESULTS: A 29-year-old immunocompetent man presented with a two-month history of photopsia and a bluish light predominantly in the left eye with onset immediately following a diagnosis of chickenpox. He subsequently developed blurring of vision in his left eye with spectral-domain optical coherence tomography showing disruption and loss of ellipsoid layer in a perivascular pattern in both eyes with fundus autofluorescence demonstrating an abnormal increase in autofluorescence predominately around the vascular arcades. Autoimmune retinopathy was suspected on the basis of the clinical presentation, electrophysiology, absence of fundus lesions, retinal degenerations or dystrophies, or intraocular inflammation and temporal association with varicella infection. Antiretinal antibody testing with Western blot and immunohistochemistry were reported to be negative, however, given the consistent evidence from all other aspects of workup and investigation the patient was commenced on a trial of prednisone. This resulted in marked reduction in photopsia and expansion of visual fields. CONCLUSION: The diagnosis of autoimmune retinopathy is ultimately clinical in nature. Despite the absence of positive retinal autoantibodies, a diagnosis of autoimmune retinopathy was made based upon consistent evidence from all other aspects of workup and investigation. This allowed prompt treatment with immunosuppressive agents with subsequent stabilization of this patient's visual function.

Variations in optic nerve head morphology by intraocular pressure in open-angle glaucoma.

PURPOSE: To compare optic disc topography in eyes in three intraocular pressure (IOP) groups of <15 mmHg, 15-20 mmHg, and ≥21 mmHg using spectral domain optical coherence tomography (SD-OCT) and confocal scanning laser ophthalmoscopy, adjusting for the degree of damage, as measured by retinal nerve fiber layer (RNFL) thickness and average visual field loss. METHODS: A total of 184 eyes of 112 patients with primary open-angle glaucoma were recruited into groups based on baseline untreated intraocular pressure (IOP) of <15 mmHg (normal-tension glaucoma [NTG], very low), 15-20 mmHg (NTG, medium), or ≥21 mmHg (high-tension glaucoma [HTG]). Patients underwent scanning laser ophthalmoscopy, SD-OCT, and Humphrey visual field testing. Univariate and multivariate models were created, accounting for degree of retinal ganglion cell (RGC) loss by either OCT RNFL thickness or visual field mean deviation (MD). RESULTS: Univariate and multivariate analyses demonstrated no morphological differences in HRT or OCT parameters among IOP groups that met Bonferroni-corrected statistical significance when using either MD or OCT RNFL as the damage criterion (p < 0.0063). The mean cup depth was shallower for the IOP <15 mmHg group than the IOP ≥21 mmHg group (p < 0.05) for both MD (p < 0.011) and OCT RNFL (p < 0.014). CONCLUSION: Normal-tension and high-tension glaucoma are not distinguishable by optic nerve head topography with HRT and OCT when the degree of damage by Humphrey visual field testing is taken into account.

Symptomatic intracranial hypertension during recovery from the syndrome of headache with neurologic deficits and cerebrospinal fluid lymphocytosis (HANDL).

The syndrome of headache with neurologic deficits and cerebrospinal fluid lymphocytosis (HANDL) is rare; it comprises migrainous headaches (generally in headache-naïve people), fluctuating neurological symptoms and cerebrospinal fluid (CSF) lymphocytosis. The syndrome generally runs a benign, self-limiting course over weeks. A small proportion of patients develop intracranial hypertension as a consequence of the illness. Recurrence of headaches or development of visual symptoms following apparent recovery from HANDL should prompt urgent re-evaluation for elevated intracranial pressure. Short-to-medium term management with CSF drainage and acetazolamide may be necessary to prevent visual loss.

Glaucoma as a neurodegenerative disease.

BACKGROUND: The primary pathophysiological feature of glaucoma is a progressive optic neuropathy with characteristic morphological changes of the optic disc and risk factors of age and intraocular pressure. Recently, involvement of other areas of the central nervous system (CNS) beyond the optic nerve has been demonstrated. This article addresses the proposition that glaucoma shares mechanistic and pathophysiologic features with neurodegenerations in the CNS. METHODS: The literature on CNS alterations in patients with glaucoma is reviewed with particular focus on neuroimaging and pathological studies. A theoretical framework for assessing whether glaucoma is truly a neurodegenerative disease is developed based on the comparison with neurodegenerative and nonneurodegenerative diseases. RESULTS: Although there is convincing evidence of abnormalities in CNS regions distal to the optic nerve in glaucoma, these are similar to those seen in other disorders of the proximal visual pathways, such as other optic neuropathies or retinal diseases. Similarly, features of glaucoma that are similar to neurodegenerations are also seen in nonneurodegenerative diseases. CONCLUSIONS: Glaucoma is less likely a primary neurodegeneration affecting the CNS and more likely a primary optic neuropathy with secondary effects in the CNS.

Functional effects of unilateral open-angle glaucoma on the primary and extrastriate visual cortex.

The purpose of this study was to use functional magnetic resonance imaging (fMRI) to investigate the response of the visual cortex to unilateral primary open-angle glaucoma (POAG). Specifically, we assessed whether regions of V1 and V2 with lost input from the glaucomatous eye had a greater response to input from the nonaffected fellow eye. Nine participants with unilateral POAG causing paracentral visual field defects and four controls participated in the study. We found no evidence for an increased response to the fellow eye in glaucoma-affected regions of the visual cortex; however, in agreement with previous studies, there was a pronounced, retinotopically localized reduction of activation in both the primary (V1) and extrastriate visual cortex (V2), when participants viewed through their glaucomatous eye. Our results suggest a remarkable level of stability within the adult primary and extrastriate visual cortex in response to unilateral neurodegeneration of the optic nerve.

Gap junction proteins in the light-damaged albino rat.

PURPOSE: Changes in connexin expression are associated with many pathological conditions seen in animal models and in humans. We hypothesized that gap junctions are important mediators in tissue dysfunction and injury processes in the retina, and therefore, we investigated the pattern of connexin protein expression in the light-damaged albino rat eye. METHODS: Adult Sprague-Dawley rats were exposed to intense light for 24 h. The animals were euthanized, and ocular tissue was harvested at 0 h, 6 h, 24 h, 48 h, and 7 days after light damage. The tissues were processed for immunohistochemistry and western blotting to analyze the expression of the gap junction proteins in the light-damaged condition compared to the non-light-damaged condition. Cell death was detected using the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) technique. RESULTS: Intense light exposure caused increased TUNEL labeling of photoreceptor cells. Immunocytochemistry revealed that connexin 36 (Cx36) was significantly increased in the inner plexiform layer and Cx45 was significantly decreased in the light-damaged retina. The pattern of Cx36 and Cx45 labeling returned to normal 7 days after light damage. Cx43 significantly increased in the RPE and the choroid in the light-damaged tissue, and decreased but not significantly in the retina. This elevated Cx43 expression in the choroid colocalized with markers of nitration-related oxidative stress (nitrotyrosine) and inflammation (CD45 and ionized calcium-binding adaptor molecule-1) in the choroid. CONCLUSIONS: The results suggest that connexins are regulated differently in the retina than in the choroid in response to photoreceptor damage. Changes in connexins, including Cx36, Cx43, and Cx45, may contribute to the damage process. Specifically, Cx43 was associated with inflammatory damage. Therefore, connexins may be candidate targets for treatment for ameliorating disease progression.

Differentiation of compressive from glaucomatous optic neuropathy with spectral-domain optical coherence tomography.

PURPOSE: To compare optic disc topography in eyes with compressive optic neuropathy (CON) and open-angle glaucoma (OAG) using spectral-domain (SD) optical coherence tomography (OCT) and Heidelberg retinal tomograph (HRT) (Heidelberg Engineering GmbH, Heidelberg, Germany). DESIGN: Cross-sectional, observational study. PARTICIPANTS: A total of 200 eyes from 123 patients with CON (69 eyes) or OAG (58 eyes) and controls (73 eyes). METHODS: Univariate and multivariate analyses of HRT parameters, SD-OCT circumpapillary retinal nerve fiber layer (RNFL) thickness, and optic nerve head (ONH) parameters. MAIN OUTCOME MEASURES: Circumpapillary RNFL, OCT ONH parameters, and HRT parameters. RESULTS: The univariate analysis of OCT parameters demonstrated significant differences between the temporal and nasal quadrants; clock hours 3 (55 vs. 73 µm), 4, 8 (93.9 vs. 70.7 µm), 9, and 10; vertical cup-to-disc ratio (C:D) (0.6 vs. 0.8) and cup volume (0.2 vs. 0.5) (P<0.001) between patients with CON and OAG, respectively. The CON discs were significantly different from normal discs for all OCT parameters except cup volume. The CON discs were not significantly different from normal discs for HRT parameters, except for mean RNFL thickness and cup shape measure. The OAG discs were significantly different from normal discs in all HRT and OCT parameters (P<0.001). Multivariate analysis demonstrated that the OCT 3 o'clock temporal sector, average C:D ratio, vertical C:D ratio, and cup volume measurements were able to differentiate OAG from CON. CONCLUSIONS: Compressive optic neuropathy is associated with significantly thinner nasal and temporal sectors compared with OAG, whereas OAG results in larger cups and cup volume with OCT measurements. The Heidelberg retinal tomograph is not able to differentiate CON from normal discs.