Neuro-ophthalmic Diseases Research Articles

ChatGPT Assisting Diagnosis of Neuro-Ophthalmology Diseases Based on Case Reports

Background: To evaluate the accuracy of Chat Generative Pre-Trained Transformer (ChatGPT), a large language model (LLM), to assist in diagnosing neuro-ophthalmic diseases based on case reports. Methods: We selected 22 different case reports of neuro-ophthalmic diseases from a publicly available online database. These cases included a wide range of chronic and acute diseases commonly seen by neuro-ophthalmic subspecialists. We inserted each case as a new prompt into ChatGPTs (GPT-3.5 and GPT-4) and asked for the most probable diagnosis. We then presented the exact information to 2 neuro-ophthalmologists and recorded their diagnoses, followed by comparing responses from both versions of ChatGPT. Results: GPT-3.5 and GPT-4 and the 2 neuro-ophthalmologists were correct in 13 (59%), 18 (82%), 19 (86%), and 19 (86%) out of 22 cases, respectively. The agreements between the various diagnostic sources were as follows: GPT-3.5 and GPT-4, 13 (59%); GPT-3.5 and the first neuro-ophthalmologist, 12 (55%); GPT-3.5 and the second neuro-ophthalmologist, 12 (55%); GPT-4 and the first neuro-ophthalmologist, 17 (77%); GPT-4 and the second neuro-ophthalmologist, 16 (73%); and first and second neuro-ophthalmologists 17 (77%). Conclusions: The accuracy of GPT-3.5 and GPT-4 in diagnosing patients with neuro-ophthalmic diseases was 59% and 82%, respectively. With further development, GPT-4 may have the potential to be used in clinical care settings to assist clinicians in providing quick, accurate diagnoses of patients in neuro-ophthalmology. The applicability of using LLMs like ChatGPT in clinical settings that lack access to subspeciality trained neuro-ophthalmologists deserves further research.

Imaging the brain: diagnosis aided by structural features on neuroimaging studies.

The use of neuroimaging allows the ophthalmologist to identify structural lesions in the orbit or along the neuroaxis that allow for more accurate diagnosis and treatment of patients with neuro-ophthalmic diseases. The primary imaging tools include computed tomography (CT) and magnetic resonance imaging (MRI), both of which can be used to evaluate the brain, spinal cord and canal, and orbits. Neurovascular structures, both arterial and venous, also can be imaged in high resolution with modern CT and MR angiography and CT and MR venography. In many cases, invasive procedures such as catheter angiography can be avoided with these studies, and angiography is often reserved for confirmation of vascular lesions combined with endovascular treatment. In this article, we illustrate how the evaluation of patients presenting with neuro-ophthalmic diseases involving the afferent and efferent visual pathways can be optimized with the use of appropriate diagnostic imaging studies. The complementary value of ophthalmic imaging is also demonstrated, and the advantages and disadvantages of both CT and MRI as well as their use in longitudinal patient follow up is demonstrated.

Utility of ChatGPT for Automated Creation of Patient Education Handouts: An Application in Neuro-Ophthalmology.

Patient education in ophthalmology poses a challenge for physicians because of time and resource limitations. ChatGPT (OpenAI, San Francisco) may assist with automating production of patient handouts on common neuro-ophthalmic diseases. We queried ChatGPT-3.5 to generate 51 patient education handouts across 17 conditions. We devised the "Quality of Generated Language Outputs for Patients" (QGLOP) tool to assess handouts on the domains of accuracy/comprehensiveness, bias, currency, and tone, each scored out of 4 for a total of 16. A fellowship-trained neuro-ophthalmologist scored each passage. Handout readability was assessed using the Simple Measure of Gobbledygook (SMOG), which estimates years of education required to understand a text. The QGLOP scores for accuracy, bias, currency, and tone were found to be 2.43, 3, 3.43, and 3.02 respectively. The mean QGLOP score was 11.9 [95% CI 8.98, 14.8] out of 16 points, indicating a performance of 74.4% [95% CI 56.1%, 92.5%]. The mean SMOG across responses as 10.9 [95% CI 9.36, 12.4] years of education. The mean QGLOP score suggests that a fellowship-trained ophthalmologist may have at-least a moderate level of satisfaction with the write-up quality conferred by ChatGPT. This still requires a final review and editing before dissemination. Comparatively, the rarer 5% of responses collectively on either extreme would require very mild or extensive revision. Also, the mean SMOG score exceeded the accepted upper limits of grade 8 reading level for health-related patient handouts. In its current iteration, ChatGPT should be used as an efficiency tool to generate an initial draft for the neuro-ophthalmologist, who may then refine the accuracy and readability for a lay readership.

An overview of neuro-ophthalmic disorders at Jenna Ophthalmic Center, Baghdad, Iraq (2021-2022).

Neuro-ophthalmic disorders are often documented individually for each illness, with little data available on their overall incidence and pattern. The overall incidence of neuro-ophthalmic illnesses in Iraq is still not recorded. This study aimed to evaluate the clinical, demographic, and etiological features of patients seeking consultation at an Iraqi neuro-ophthalmology clinic. A prospective cross-sectional observational research was conducted at the Janna Ophthalmic Center in Baghdad, Iraq. The center serves a diverse patient population from various governorates. All newly diagnosed patients with neuro-ophthalmic disorders who visited the neuro-ophthalmological clinic, regardless of gender or age group, were included. The neuro-ophthalmologist established a diagnosis for each case by reviewing the patient's medical history, doing physical examinations, administering specific tests, and, in certain cases, using neuroimaging methods. The duration of the study was extended from March 2021 to November 2022. Among the 6440 patients evaluated, 613 cases were confirmed at the neuro-ophthalmology clinic. Ischemic optic neuropathy (NAION, AION, and PION) was the most prevalent diagnosis, accounting for 17.61% of newly reported cases in the field of neuro-ophthalmology. This was followed by sixth nerve palsy. Diabetes mellitus affected 42.7% of the cases, followed by hypertension, which affected 39.3% of the participants. The incidence of neuro-ophthalmic diseases tended to be high. Ischemic optic neuropathy and sixth nerve palsy, traumatic/compressive optic neuropathy, and papilledema were the most common neuro-ophthalmic disorders reported.

Rapid measurement and machine learning classification of colour vision deficiency.

Colour vision deficiencies (CVDs) indicate potential genetic variations and can be important biomarkers of acquired impairment in many neuro-ophthalmic diseases. However, CVDs are typically measured with tests which possess high sensitivity for detecting the presence of a CVD but do not quantify its type or severity. In this study, we introduce Foraging Interactive D-prime (FInD), a novel computer-based, generalisable, rapid, self-administered vision assessment tool and apply it to colour vision testing. This signal detection theory-based adaptive paradigm computed test stimulus intensity from d-prime analysis. Stimuli were chromatic Gaussian blobs in dynamic luminance noise, and participants clicked on cells that contained chromatic blobs (detection) or blob pairs of differing colours (discrimination). Sensitivity and repeatability of FInD colour tasks were compared against the Hardy-Rand-Rittler and the Farnsworth-Munsell 100 hue tests in 19 colour-normal and 18 inherited colour-atypical, age-matched observers. Rayleigh colour match was also completed. Detection and discrimination thresholds were higher for atypical than for typical observers, with selective threshold elevations corresponding to unique CVD types. Classifications of CVD type and severity via unsupervised machine learning confirmed functional subtypes. FInD tasks reliably detect inherited CVDs, and may serve as valuable tools in basic and clinical colour vision science.

Impact of COVID-19 on Neuro-Ophthalmology in the United States: A National Survey.

To evaluate the impacts of the COVID-19 on neuro-ophthalmology practice in the United States. Cross-sectional study. The North American Neuro-ophthalmology Society distributed a survey on the impact of COVID-19 on neuro-ophthalmic practice to its members. The survey consisted of 15 questions regarding the impact of the pandemic on neuro-ophthalmic practice and perspectives. Twenty-eight neuro-ophthalmologists practicing in the United States responded to our survey. In this survey, 64% of survey respondents were male (n = 18), while 36% were female (n = 10). The average age of a respondent was 55 years old. According to 77% of survey respondents, various neuro-ophthalmic diseases were reported to have worsened during the pandemic including idiopathic intracranial hypertension, compressive optic neuropathy, optic neuritis, and giant cell arteritis. This survey represents one of the largest studies to describe the impact of the COVID-19 pandemic of neuro-ophthalmology. Given the underrepresentation of neuro-ophthalmology in the United States as described in the literature, this study strengthens the need for more neuro-ophthalmologists to provide timely care, particularly during the pandemic. Further interventions to incentivize the pursuit of neuro-ophthalmology training may help combat the effects of COVID-19 on neuro-ophthalmic conditions.

Morphometric Analysis of Retinal Ganglion Cell Axons in Normal and Glaucomatous Brown Norway Rats Optic Nerves.

A reference atlas of optic nerve (ON) retinal ganglion cell (RGC) axons could facilitate studies of neuro-ophthalmic diseases by detecting subtle RGC axonal changes. Here we construct an RGC axonal atlas for normotensive eyes in Brown Norway rats, widely used in glaucoma research, and also develop/evaluate several novel metrics of axonal damage in hypertensive eyes. Light micrographs of entire ON cross-sections from hypertensive and normotensive eyes were processed through a deep learning-based algorithm, AxoNet2.0, to determine axonal morphological properties and were semiquantitatively scored using the Morrison grading scale (MGS) to provide a damage score independent of AxoNet2.0 outcomes. To construct atlases, ONs were conformally mapped onto an ON "template," and axonal morphometric data was computed for each region. We also developed damage metrics based on myelin morphometry. In normotensive eyes, average axon density was ∼0.3 axons/µm2 (i.e., ∼80,000 axons in an ON). We measured axoplasm diameter, eccentricity, cross-sectional area, and myelin g-ratio and thickness. Most morphological parameters exhibited a wide range of coefficients of variation (CoV); however, myelin thickness CoV was only ∼2% in normotensive eyes. In hypertensive eyes, increased myelin thickness correlated strongly with MGS (P < 0.0001). We present the first comprehensive normative RGC axon morphometric atlas for Brown Norway rat eyes. We suggest objective, repeatable damage metrics based on RGC axon myelin thickness for hypertensive eyes. These tools can evaluate regional changes in RGCs and overall levels of damage in glaucoma studies using Brown Norway rats.

The location diagnostic value of morphologic features of macular ganglion cell complex thickness in optic pathway-related neuro-ophthalmology

The current study analyzed the morphologic features of macular ganglion cell complex (mGCC) thickness in optic pathway-related neuro-ophthalmic diseases by swept-source optical coherence tomography (SS-OCT). mGCC has the location diagnostic value similar to visual field, and the distribution of macular ganglion cells has accurate horizontal, vertical and quadrant characteristics. Specifically, prechiasmatic lesions showed atrophy and thinning of mGCC ring in single eye or mGCC atrophy in the upper and lower half of horizontal demarcation, chiasmatic lesions exhibited atrophy and thinning of mGCC in the half of bilateral nasal side demarcated by mid-vertical line, and retrochiasmatic lesions presented with atrophy of mGCC in the half of mid-vertical line demarcated or 1/4 quadrant. Therefore, the morphological characteristics of mGCC thickness are of value in the location diagnosis of optic path-related neuro-ophthalmic diseases.

Accommodation

Accommodation is the natural increase or decrease of the refraction of the eye lens as a function of the fixation distance. It relies on the proper elasticity of the natural eye lens. The evaluation of accommodation and the coupled convergent eye movements enables us to make the diagnosis of certain eye-related conditions and allows the differential diagnostic from some of the "neuroophthalmic diseases". This may avoid some unnecessary diagnostic procedures and reduce patient anxiety in terms of having a health threatening disease.

The Eye Is a Window to Systemic and Neuro-Ophthalmic Diseases.

The Eye Is a Window to Systemic and Neuro-Ophthalmic Diseases.

Invasive Fungal Sinusitis in Patients With Coronavirus Disease 2019 Seen in South India.

Coronavirus disease 2019 (COVID-19) has a vast array of presentations and associations with neuro-ophthalmic diseases. There has been a recent surge in ophthalmic manifestations secondary to fungal sinus infections in India especially in diabetic patients who were given systemic steroids. We present our COVID-19-related cranial neuropathies presenting in our clinic. This is a retrospective case series of 10 patients affected with COVID-19 disease and who presented with cranial nerve palsies at the neuro-ophthalmic department of a tertiary eye care hospital in South India. An analysis of electronic medical records data was performed, including their comorbidities, symptoms, cranial nerves involved, ocular and neuroimaging findings, site of lesion, etiology, and prognosis. Most of the patients (7 of 10) presented with multiple cranial nerve palsies (MCNP) with poor visual acuity. 2 of the 10 cases succumbed to death due to the intracranial involvement. All MCNP cases had uncontrolled diabetes with a history of systemic steroids, and neuroimaging of these cases showed sinusitis of varying severity most of which were suggestive of fungal invasive type. Our study emphasizes the need to screen for fungal involvement in COVID-19 cases presenting with MCNP especially on diabetic patients on systemic steroids so that an early diagnosis may reduce visual loss and mortality. Physicians treating COVID-19 cases need to be aware of this dreadful complication.

English

BACKGROUND Visual field defects are caused by different lesions affecting different sites of visual pathway. Most common causes include stroke and intracranial space occupying lesions. Assessment of visual field defect helps in localization of the lesion along with measurement of the defect. The purpose of this study was to record different types of visual field defects in neuro-ophthalmic diseases. METHODS This cross-sectional observational study was conducted between February 2016 and March 2018 at Department of Ophthalmology, SVRRGG Hospital. Visual field testing was done by confrontation method and Humphreys field analyser with best corrected visual acuity. Patient satisfying inclusion and exclusion criteria are included in the study. RESULTS Among the 58 participants, 37 (64 %) were males and 21 (36%) were females. Cerebrovascular accident was seen in 25 cases which was the most common aetiology followed by pituitary adenomas in 14 cases. Complete homonymous hemianopia was observed in 16 cases which was the most common field defect followed by bi-temporal hemianopia in 12 cases, enlargement of blind spot in 11 cases, incomplete homonymous hemianopia in 7 cases, superior and inferior quadrantanopia in 4 cases each, inferior altitudinal field defects in 2 cases, central scotomas in two cases and superior altitudinal field defect in one case. CONCLUSIONS Visual field defects are used to monitor the progression, recurrence of disease and as a guide for treatment. It is mandatory to record the fields in the neuroophthalmic diseases. KEY WORDS Visual Field Defects, Neuro-Ophthalmic Diseases

Impact of lockdown during the COVID-19 outbreak on ophthalmological emergencies in a referral center in France

PurposeIn March 2020, the sudden rise in the number of SARS-CoV-2 infections in France led the government to impose a strict lockdown during which all non-urgent medical consultations were postponed. From March 17 to May 10, 2020, private medical practices were closed, and telemedicine was encouraged. The consequences on ophthalmic care were dramatic, with over 90% of scheduled consultations canceled. The goal of this study was to describe consultations during the 2-month strict lockdown in Paris and to analyze its impact on the visual outcomes of patients consulting in the ophthalmology emergency department (OED).MethodsData of patients who presented to the OED of the A. de Rothschild Foundation Hospital (RFH), a tertiary ophthalmology center in Paris, France, during the lockdown period and its immediate aftermath were analyzed. The results were compared to the same time periods in the years 2018 and 2019. Four time periods were defined and numbered chronologically: March 17 to May 10, 2018 (period 1); March 17 to May 10, 2019 (period 2); March 17 to May 10, 2020 (period 3, the lockdown period); May 11 to June 9, 2020 (period 4, the post-lockdown period).ResultsThe number of consultations was reduced by more than 50% during the lockdown period (n = 2909 patients) and by 30% during the post-lockdown period (n = 2622) when compared to periods 1 (n = 7125) and 2 (n = 8058). Even though LP4 saw an increase in the number of patients consulting, there was no increase in the rate of severe diseases (12.8% during LP3 vs. 11.1% during LP4), and the proportion of patients who were admitted was statistically similar (4.3% vs. 3.6%). Neuro-ophthalmic diseases were the most common during LP3 and LP4. Neovascular glaucoma was twice as common during post-LP4 (P = 0.08). We noted a significant increase in patients with graft rejection consulting in our OED during the post-LP4 (P < 0.001). These results were likely related to a delay in follow-up consultations due to the lockdown measures.ConclusionThe reduction in the number of consultations in our OED during the lockdown period affected both minor emergencies and severe ophthalmic diseases, but with no significant delay in diagnosis. More longitudinal and longer study is needed to confirm this and to retrospectively analyze the effects of the COVID-19 outbreak and lockdown.

A haploscope based binocular pupillometer system to quantify the dynamics of direct and consensual Pupillary Light Reflex

This study described the development of a haploscope-based pupillometer for the parametrization of the Pupillary Light Reflex (PLR), and its feasibility in a set of 30 healthy subjects (light or dark-colored irides) and five patients diagnosed with Relative Afferent Pupillary Defect (RAPD). Our supplementary aim focused on evaluating the influence of iris colour on the PLR to decide whether a difference in PLR parameters should be anticipated when this system is used across ethnicities. All the participants underwent a customized pupillometry protocol and the generated pupil traces, captured by an eye tracker, were analyzed using exponential fits to derive PLR parameters. A Pupil Response Symmetry (PRS) coefficient was calculated to predict the presence of RAPD. The mean (SD) Initial PD during dilation (3.2 (0.5) mm) and the minimum PD during constriction (2.9 (0.4) mm) in the light iris group had a statistically significant (p < 0.001) higher magnitude compared to the dark iris group. The normal limits of the PRS coefficient ranged from − 0.20 to + 1.07 and all RAPD patients were outside the calculated normal limits. This proposed system, analysis strategies, and the tested metrics showed good short-term repeatability and the potential in detecting pupil abnormalities in neuro-ophthalmic diseases.

Clinical and genetic charsteristics of the Bosch–Boonstra–Schaaf syndrome due to novel mutations in the &lt;i&gt;NR2F1&lt;/i&gt; gene

Bosch–Boonstra–Schaaf optic atrophy is autosomal dominant disorder caused by mutations in the NR2F1 gene. Its common features include optic atrophy and / or hypoplasia, developmental delay, intellectual disability, attention deficit disorder, autism spectrum disorder, seizures, hearing defects, spasticity, hypotonia, and thinning of the corpus callosum. We report of the clinical and genetic characteristics of two patients with Bosch-Boonstra-Schaaf syndrome with newly detected of the missense mutations с.329T&gt;C (p.Phe110Ser) and с.413G&gt;A (p.Cys138Tyr) in the gene NR2F1. The existence of a polymorphism of the clinical manifestations of the syndrome has been shown, and the necessity of using exome sequencing in the diagnosis of neuro-ophthalmic diseases has been substantiated.

Potential neuroprotective biomolecules in ophthalmology.

Retinal neurodegenerative diseases are responsible for a huge number of ocular problems worldwide. It seems that the progression of these diseases can be managed by the application of neuroprotective molecules particularly in the early stages. This article focuses on the most common neuroprotective bioagents under investigation in ophthalmology. We searched the web of science, PubMed and Scopus databases with these keywords: "glaucoma," "diabetic retinopathy," "age-related macular degeneration," "optic neuropathy and retinal degeneration" and/or "neuroprotection." The most commonly utilized neuroprotective drugs for ophthalmology diseases were introduced in this study. It seems that these agents can be divided into three categories according to their mechanism of action: (A) neurotrophins, (B) decreasing effect on intraocular pressure and (C) inhibition of retinal neuron apoptosis. A broad range of drugs has been illustrated in the literature for treatment of neuro-ophthalmic diseases. A good classification of the most applied drugs in this field can help specialists to prescribe the best matched drug considering the stage and progression of disease. However, controlled clinical trials are needed for better evaluation of the effects of these products.

Big Data Research in Neuro-Ophthalmology: Promises and Pitfalls.

Big data clinical research involves application of large data sets to the study of disease. It is of interest to neuro-ophthalmologists but also may be a challenge because of the relative rarity of many of the diseases treated. Evidence for this review was gathered from the authors' experiences performing analysis of large data sets and review of the literature. Big data sets are heterogeneous, and include prospective surveys, medical administrative and claims data and registries compiled from medical records. High-quality studies must pay careful attention to aspects of data set selection, including potential bias, and data management issues, such as missing data, variable definition, and statistical modeling to generate appropriate conclusions. There are many studies of neuro-ophthalmic diseases that use big data approaches. Big data clinical research studies complement other research methodologies to advance our understanding of human disease. A rigorous and careful approach to data set selection, data management, data analysis, and data interpretation characterizes high-quality studies.

Reduced Visual Quality of Life Associated with Migraine is Most Closely Correlated with Symptoms of Dry Eye.

Patients with migraine frequently report ocular or visual symptoms including aura, photophobia, and eye pain. Using validated instruments, our group previously reported that due to these symptoms, patients have marked reductions in visual quality of life. In chronic migraine, these reductions can be as substantial as those reported for other neuro-ophthalmic diseases such as multiple sclerosis with optic neuritis and idiopathic intracranial hypertension. Because the instruments take several different dimensions into account, we were unable to determine which ocular symptom(s) contributed to reduced visual quality of life. The purpose of this investigation was to attempt to determine which ocular symptom(s) were driving the observed reduction in visual quality of life. We designed a cross-sectional survey-based study to assess visual quality of life, headache impact, aura, dry eye, and photophobia in migraine patients. Subjects were recruited from the Headache Clinic and General Neurology Clinic at a tertiary teaching hospital. Subjects completed validated questionnaires including: The visual functioning questionnaire-25 (VFQ-25), the headache impact test (HIT-6), the visual aura rating scale (VARS), the ocular surface disease index (OSDI), and the Utah photophobia score (UPSIS-17). Associations between VFQ-25 and OSDI, VFQ-25 and VARS, VFQ-25 and UPSIS-17, HIT-6 and OSDI, HIT-6 and VARS, and HIT-6 and UPSIS-17 were calculated. Of the 62 patients who completed all questionnaires, 17 had episodic migraine and 45 had chronic migraine. Twenty-three patients experienced aura and 39 did not report aura. The most striking correlations were observed between the VFQ-25 and the OSDI (-0.678; P<.001), between the HIT-6 and UPSIS-17 (0.489; P<.001), and between the HIT-6 and OSDI (0.453; P<.001). Dry eye seems to be the most important symptom that reduces visual quality of life and worsens headache impact. This symptom may be a form of allodynia, a well-known feature of chronic migraine. Photophobia appears to have modest effects on headache impact. In the future, we hope to determine whether treatment of dry eye symptoms can improve visual quality of life and reduce headache impact.

Value of Optical Coherence Tomography Angiography in Neuroophthalmology

Within the last few years, optical coherence tomography angiography (OCTA) has been one of the most intensively investigated developments in ophthalmic research. As a non-invasive imaging tool, it can visualise retinal, choroidal and peripapillary blood flow and was first introduced in retinology. Recently, OCTA has received increasing attention in neuro-ophthalmological diagnostic testing. Special consideration has been given to diseases in which vascular pathogenesis is discussed, such as non-arteritic and arteritic anterior ischemic optic neuropathy (NAION and AAION). Numerous studies have demonstrated rarefication of the peripapillary vascular network and reduced blood flow in NAION and AAION patients compared to healthy patients. The extent of the vascular damage correlates with the severity of optic atrophy. Similar findings also apply to optic atrophy from other causes (e.g., optic nerve head drusen, hereditary optic neuropathy, etc.). However, the exact causal relationships between optic neuropathy and blood flow reduction remain unclear and must be addressed in future investigations. In some diseases, OCTA also seems to be of differential diagnostic value. In haemangioblastomas, it has provided relevant information, especially in large and broad-based findings, and may represent the haemangioblastoma-typical vascular networks and the afferent vessels. This review summarises new information from OCTA studies on neuro-ophthalmic diseases, and questions their relevance and value in clinical use. In the future, it can be expected that OCTA will provide standard values through longitudinal studies with larger numbers of cases that more relevant changes in blood flow in a wide variety of clinical pictures will be analysed more profoundly and will possibly contribute to differential diagnostic and therapeutic studies.

Increased ER Stress After Experimental Ischemic Optic Neuropathy and Improved RGC and Oligodendrocyte Survival After Treatment With Chemical Chaperon.

PurposeIncreased endoplasmic reticulum (ER) stress is one of the earliest subcellular changes in neuro-ophthalmic diseases. In this study, we investigated the expression of key molecules in the ER stress pathways following nonarteritic anterior ischemic optic neuropathy (AION), the most common acute optic neuropathy in adults over 50, and assessed the impact of chemical chaperon 4-phenylbutyric acid (4-PBA) in vivo.MethodsWe induced AION using photochemical thrombosis in adult mice and performed histologic analyses of key molecules in the ER stress pathway in the retina and optic nerve. We also assessed the effects of daily intraperitoneal injections of 4-PBA after AION.ResultsIn the retina at baseline, there was low proapoptotic transcriptional regulator C/EBP homologous protein (CHOP) and high prosurvival chaperon glucose-regulated protein 78 (GRP78) expression in retinal ganglion cells (RGCs). One day after AION, there was significantly increased CHOP and reduced GRP78 expressions in the ganglion cell layer. In the optic nerve at baseline, there was little CHOP and high GRP78 expression. One day after AION, there was significantly increased CHOP and no change in GRP78 expression. Treatment immediately after AION using daily intraperitoneal injection of chemical chaperone 4-PBA for 19 days significantly rescued Brn3A+ RGCs and Olig2+ optic nerve oligodendrocytes.ConclusionsWe showed for the first time that acute AION resulted in increased ER stress and differential expression of ER stress markers CHOP and GRP78 in the retina and optic nerve. Rescue of RGCs and oligodendrocytes with 4-PBA provides support for ER stress reduction as possible treatment for AION.