Automated Classification of Physiologic, Glaucomatous, and Glaucoma-Suspected Optic Discs Using Machine Learning.

In order to generate a machine learning algorithm (MLA) that can support ophthalmologists with the diagnosis of glaucoma, a carefully selected dataset that is based on clinically confirmed glaucoma patients as well as borderline cases (e.g., patients with suspected glaucoma) is required. The clinical annotation of datasets is usually performed at the expense of the data volume, which results in poorer algorithm performance. This study aimed to evaluate the application of an MLA for the automated classification of physiological optic discs (PODs), glaucomatous optic discs (GODs), and glaucoma-suspected optic discs (GSODs). Annotation of the data to the three groups was based on the diagnosis made in clinical practice by a glaucoma specialist. Color fundus photographs and 14 types of metadata (including visual field testing, retinal nerve fiber layer thickness, and cup-disc ratio) of 1168 eyes from 584 patients (POD = 321, GOD = 336, GSOD = 310) were used for the study. Machine learning (ML) was performed in the first step with the color fundus photographs only and in the second step with the images and metadata. Sensitivity, specificity, and accuracy of the classification of GSOD vs. GOD and POD vs. GOD were evaluated. Classification of GOD vs. GSOD and GOD vs. POD performed in the first step had AUCs of 0.84 and 0.88, respectively. By combining the images and metadata, the AUCs increased to 0.92 and 0.99, respectively. By combining images and metadata, excellent performance of the MLA can be achieved despite having only a small amount of data, thus supporting ophthalmologists with glaucoma diagnosis.

Effectiveness of Strabismus Surgery in Intermittent Exotropia and Factors Influencing Outcome.

Intermittent exotropia (IXT) is known to relapse after surgery. No factors to predict or prevent recurrence are known with certainty. This study investigated surgical outcome, potential influencing factors, and reoperation rate in patients with IXT. Medical records of 537 patients who underwent surgery for IXT from 2000 to 2022 with preoperative angles of exodeviation of 6 to 50 prism diopters (PD) were retrospectively studied. Multivariate regression analyses of factors influencing surgical outcome on postoperative day 1 (POD1) and reoperation rate were performed. A Kaplan-Meier analysis was performed to illustrate the reoperation rate. After the first surgery, 83.8% of patients had a successful surgical outcome on POD1 (esodeviation ≤ 5 PD or exodeviation ≤ 10 PD). Logistic regression analysis revealed that small preoperative angles of exodeviation increased the probability for surgical success. Follow-up data at different times (4 days-20 years) after surgery were available for 176 patients: 40 patients were still in the range of surgical success, 133 patients had exotropia > 10 PD. Of the follow-up patients, 65 (12.1%) underwent reoperation. A total of 8.5% had their reoperation within one year after the first surgery, 52.9% within five years. Cox regression analysis revealed that large preoperative angles of exodeviation, far/near incomitance and alphabet pattern strabismus increased the risk of reoperation. Most patients achieved surgical success on POD1, yet the squint angles often increased after surgery, resulting in reoperation in some patients. Prospective studies are needed for a better assessment of pre-, peri- and postoperative factors for surgical success in IXT.

Accuracy of Bruch's membrane opening minimum rim width and retinal nerve fiber layer thickness in glaucoma diagnosis depending on optic disc size.

BACKGROUND/AIM: The aim of this paper is to compare retinal nerve fiber layer thickness (RNFL) and Bruch's membrane opening-based minimum rim width (BMO-MRW) in terms of their performance in detecting early and moderate/advanced glaucoma using receiver operating characteristics (ROC) analysis and the classification using the 5th percentile as a cut-off. METHODS: One hundred eyes from 100 patients with early glaucoma (mean deviation (MD): < -5.0 dB) and 100 eyes from 100 patients with moderate/advanced glaucoma (MD: > -5.0 dB) were carefully matched to healthy controls based on optic disc size. Then, the dataset was divided, based on the 50th percentile of the measured Bruch's membrane opening area (BMO-A), into small (BMO-A < 1.95 mm2) and large optic discs (BMO-A > 1.95 mm2). Finally, the discriminative performance of BMO-MRW and RNFL between glaucoma and controls using ROC analysis and the manufacturer's classification based on the 5th percentile was analyzed. RESULTS: In discriminating between glaucoma and matched healthy controls, global BMO-MRW and global RNFL thickness had comparable areas under the ROC curve for eyes with early glaucoma and both small BMO-As (ROC ± confidence interval [CI] 0.91 [0.87 to 0.95] and 0.88 [0.83 to 0.93]) and large BMO-As (0.86 [0.82 to 0.92] and 0.84 [0.79 to 0.90]), as well as in moderate/advanced glaucoma with small BMO-As (0.99 [0.98 to 1.00] and 0.97 [0.95 to 1.00]) and large BMO-As (0.94 [0.91 to 0.98] and 0.97 [0.94 to 1.00]). Using the calculated 5th percentile as a threshold value, the sensitivities for the detection of early and moderate/advanced glaucoma were comparable for BMO-MRW and RNFL in eyes with small optic discs (early glaucoma: fifty-two percent and 61%; moderate/advanced glaucoma: ninety-one percent and 92%). In eyes with large optic discs, the sensitivity of BMO-MRW was inferior to that of RNFL for both early (38% versus 51%) and moderate/advanced (80% versus 91%) glaucoma. CONCLUSION: Based on an ROC analysis, the discriminative performance of BMO-MRW and RNFL between patients with early and moderate/advanced glaucoma and a healthy control group matched based on optic disc size is comparable in eyes with BMO-As smaller and larger 1.95 mm2. Using a classification based on the 5th percentile, as used in clinical practice, RNFL is shown to be superior to BMO-MRW regarding sensitivity in glaucoma detection with large optic discs. This study underscores the importance of RNFL imaging and measurement in the diagnostic evaluation of glaucoma, especially in cases of large optic discs.

Acute Idiopathic Blind Spot Enlargement Syndrome (AIBSES) in the Era of OCT - a Review. / Acute Idiopathic Blind Spot Enlargement Syndrome (AIBSES) ­ Nutzen der OCT: Übersichtsarbeit.

There are only about 100 case reports on the Acute Idiopathic Blind Spot Enlargement Syndrome (AIBSES). This is characterised by the eponymous visual field loss in the blind spot area, acute onset photopsia, and funduscopically little or no change in the optic disc area, with conspicuous outer retinal bands on optical coherence tomography (OCT). Typical is the unilateral occurrence. Predominantly young women are affected. While previous reviews of AIBSES either predate the introduction of OCT or focus on differentiation from potentially related outer retinal conditions (e.g., multiple evanescent white dot syndrome and acute zonal occult outer retinopathy), the present review will concentrate on the current perspective and treatment strategies that have been developed and will aim to help increase awareness. Since the first description of AIBSES in the late 1980s, the introduction of OCT has simplified the diagnosis and characterisation of AIBSES as a disease of the outer retina. Nevertheless, misdiagnosis remains common in the spectrum of optic neuritis, as AIBSES may be ignored in differential diagnosis.

Evaluation of Retinal Nerve Fiber Layer and Macular Ganglion Cell Layer Thickness in Relation to Optic Disc Size.

To investigate whether optic nerve ganglion cell amount is dependent on optic disc size, this trial analyzes the correlation between Bruch's membrane opening area (BMOA) and retinal nerve fiber layer (RNFL) thickness as well as macular ganglion cell layer thickness (mGCLT). Additionally, differences in RNFL and mGCLT regarding various optic disc cohorts are evaluated. This retrospective, monocentric study included 501 healthy eyes of 287 patients from the University Hospital Münster, Germany, who received macular and optic disc optical coherence tomography (OCT) scans. Rank correlation coefficients for clustered data were calculated to investigate the relationship between BMOA and thickness values of respective retinal layers. Furthermore, these values were compared between different optic disc groups based on BMOA. Statistical analysis did not reveal a significant correlation between BMOA and RNFL thickness, nor between BMOA and mGCLT. However, groupwise analysis showed global RNFL to be significantly decreased in small and large discs in comparison to medium discs. This was not observed for global mGCLT. This study extends existing normative data for mGCLT taking optic disc size into account. While the ganglion cell amount represented by the RNFL and mGCLT seemed independent of BMOA, mGCLT was superior to global RNFL in displaying optic nerve integrity in very small and very large optic discs.

Low-dose AtropIne for Myopia Control in Children (AIM): protocol for a randomised, controlled, double-blind, multicentre, clinical trial with two parallel arms.

INTRODUCTION: Myopia is a major cause of degenerative eye disease and increases the risk of secondary visual impairment. Mitigating its progression therefore has great potential of clinically relevant benefit as shown by using highly diluted atropine eye drops in children of Asian origin. However, limited evidence is available regarding the efficacy and safety of low-dose atropine therapy in non-Asian populations. Hence, the Low-dose AtropIne for Myopia Control in Children (AIM) study will test the efficacy and safety of 0.02% atropine vs placebo in a German population. METHODS AND ANALYSIS: AIM is a national, multicentre, prospective, randomised, placebo-controlled, double-blind trial with two parallel arms. The primary objective is to assess the efficacy of atropine 0.02% eyedrops for myopia control in children of Caucasian origin. The primary outcome is the change in cycloplegic refraction after 1 year of treatment (D/year). Secondary and tertiary outcome measures comprise the change in axial length (mm/year) in children treated with 0.02% atropine compared with placebo, the myopic progression of participants treated with 0.01% compared with 0.02% atropine (D/year and mm/year), and the safety profile of both 0.02% and 0.01% atropine. Furthermore, the myopic progression 1 year after cessation of therapy with 0.02% atropine will be evaluated. Inclusion criteria are an age of 8-12 years and myopia of -1 D to -6 D with an estimated annual myopia progression of ≥0.5 D. After randomisation, patients will receive either atropine 0.02% (arm A) or placebo eye drops (arm B) in the first year of treatment. In the second year, they will continue to receive atropine 0.02% (arm A) or switch to atropine 0.01% (arm B). In the third year, they will switch to placebo (arm A) or continue with atropine 0.01% (arm B). To achieve a statistical power of 80%, the calculated sample size is 300. The trial has started in October 2021 with a planned recruitment period of 18 months. ETHICS AND DISSEMINATION: AIM has been approved by the Central Ethics Committee of the University Medical Center Freiburg (21-1106), local ethics committees of each participating centre and the German Federal Institute for Drugs and Medical Devices (61-3910-4044659). It complies with the Declaration of Helsinki, local laws and ICH-GCP. Results and underlying data from this trial will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT03865160.

Optical Coherence Tomography as a Biomarker for Differential Diagnostics in Nystagmus: Ganglion Cell Layer Thickness Ratio.

In albinism, with the use of optical coherence tomography (OCT), a thinning of the macular ganglion cell layer was recently reported. As a consequence, the relevant OCT measure, i.e., a reduction of the temporal/nasal ganglion cell layer thickness quotient (GCLTQ), is a strong candidate for a novel biomarker of albinism. However, nystagmus is a common trait in albinism and is known as a potential confound of imaging techniques. Therefore, there is a need to determine the impact of nystagmus without albinism on the GCLTQ. In this bi-center study, the retinal GCLTQ was determined (OCT Spectralis, Heidelberg Engineering, Heidelberg, Germany) for healthy controls (n = 5, 10 eyes) vs. participants with nystagmus and albinism (Nalbinism, n = 8, 15 eyes), and with nystagmus of other origins (Nother, n = 11, 17 eyes). Macular OCT with 25 horizontal B scans 20 × 20° with 9 automated real time tracking (ART) frames centered on the retina was obtained for each group. From the sectoral GCLTs of the early treatment diabetic retinopathy study (ETDRS) circular thickness maps, i.e., 3 mm and 6 mm ETDRS rings, GCLTQ I and GCLTQ II were determined. Both GCLTQs were reduced in Nalbinism (GCLTQ I and II: 0.78 and 0.77, p < 0.001) compared to Nother (0.91 and 0.93) and healthy controls (0.89 and 0.95). The discrimination of Nalbinism from Nother via GCLTQ I and II had an area under the curve of 80 and 82% with an optimal cutoff point of 0.86 and 0.88, respectively. In conclusion, lower GCLTQ in Nalbinism appears as a distinguished feature in albinism-related nystagmus as opposed to other causes of nystagmus.

Acute Idiopathic Blind Spot Enlargement Syndrome-New Perspectives in the OCT Era.

Acute idiopathic blind spot enlargement syndrome (AIBSES) is characterized by unilateral visual field loss in the blind spot area, acute onset photopsia, and funduscopically few or no optic disc changes. AIBSES predominantly affects young adults and is often misdiagnosed as optic neuritis because of low awareness. Optical coherence tomography (OCT) has become the gold standard in diagnosing AIBSES as a disease of the outer retina. In our case series, we present three consecutive patients with AIBSES followed prospectively with and without steroid therapy. The patients, aged 25 to 27 years, presented in our neuroophthalmology department between 2020 and 2021. We report their disease course and management and discuss therapeutic options, as no well-established procedures exist. Common pitfalls and diagnostic errors are analysed. Two women and one man showed unilateral acute-onset photopsia and blind spot enlargement on perimetry without visual acuity reduction. Spectral domain OCT (Heidelberg Engineering, Heidelberg, Germany) revealed marked peripapillary changes in the ellipsoid zone and autofluorescence in all patients, corresponding to faint blurring of the optic disc margin. Characteristically, there was no P100 latency delay in the visual evoked potential in any of the patients. Two patients received weight-adapted oral prednisolone, which was gradually tapered over six to eight weeks. Two patients showed full recovery of their symptoms at six and seven months after onset, while mild defect healing was seen in one treated patient after 12 months. Follow-up OCT showed restoration of the outer retinal layers 6-12 months after disease onset. Careful history taking and an unprejudiced ophthalmological workup helps in diagnosing AIBSES in young adults with unilateral acute visual field defects. While its etiology is still unclear, accurate diagnosis of AIBSES can be made with peripapillary OCT. In our cases, the disease course of AIBSES was much better than its reputation. Early corticosteroid treatment may support outer retinal reorganisation, which can be followed with OCT in accordance with visual field restoration. This should be addressed in a prospective study.

Primary Optic Disc Tumors - Case Series and Literature Overview. / Primäre Papillentumoren ­ Fallserie und Literaturüberblick.

PURPOSE: Primary optic disc tumors are often a challenge for ophthalmologists. They have very different appearances, and many primary optic disc tumors are associated with syndromic diseases (especially phakomatoses). Because of the rarity of primary optic disc tumors, classification and assessment are often difficult. MATERIAL AND METHODS: A systematic search in the electronic patient files (period 01.01.2015 - 01.06.2022) of the Department of Ophthalmology of the University of Münster Medical Center for patients with primary optic disc tumors was performed. For each tumor entity, exemplary cases were selected, which are presented here in detail. The criteria for the exemplary case selection were a clear diagnosis, the presence of suitable image material and follow-up examinations in our clinic. RESULTS: The search yielded seven cases with three different primary tumor entities in the optic disc region (capillary hemangioblastoma, astrocytic hamartoma and melanocytoma). Four patients were selected as examples and are presented here: two cases for capillary hemangioblastoma (one isolated and the other in the context of Von-Hippel-Lindau syndrome) and one case each for astrocytic hamartoma and melanocytoma). We outline the further diagnosis and the course of the disease and we give an overview of the essential features of the underlying tumors in each case. CONCLUSION: The knowledge of the different primary tumors of the optic disc is necessary for a correct diagnosis and for the differentiation from malignant processes and optic disc anomalies. In many cases, further interdisciplinary diagnostics are necessary. Multimodal imaging is helpful and a referral to a center for ocular tumors is worth considering.

Treating Severe Pediatric Keratoconjunctivitis with Topical Cyclosporine A. / Behandlung der chronischen Keratokonjunktivitis im Kindesalter mit topischem Ciclosporin A.

The incidence of chronic keratoconjunctivitis, which potentially causes long-term loss of visual acuity due to corneal opacity, is considerably less common in children than in adults. It is therefore in danger of being overlooked. In children the appropriate treatment is therefore often introduced too late, or to an insufficient extent. In this article we would like to raise awareness about the diagnosis of chronic keratoconjunctivitis in children, and to present an effective treatment plan for severe stages of the disease. There are two forms of chronic keratoconjunctivitis that occur most frequently in children: hyperergic blepharokeratoconjunctivitis (hBKC) and vernal keratoconjunctivitis (VKC). With hBKC, the patient often has a history of recurring hordeolum and also presents with blepharitis; it is characterized by the marked presence of corneal neovascularization in the lower circumference of the cornea. VKC is typically characterized by changes under the upper eyelid, with marked changes to the superior limbus. If there is a risk of complications involving the cornea, or in the presence of such complications, a consistent long-term topical immunosuppressive and anti-inflammatory treatment is required. Both of these properties are combined in the active ingredient cyclosporine A. Other advantages of topical CSA treatment are its steroid-sparing effect and the long-term reduction of exacerbations. Parents need to be informed about the chronic nature of these two diseases and their tendency to recur; because of these characteristics, treatment, in most cases, should be envisaged for at least one year in order to effectively disrupt the complex immunologic processes. This safeguards the child's visual development and prevents amblyopia caused by scarring and astigmatism. We hope that the data presented will lower the barriers related to prescribing CSA for topical eye application in children.

Surgical outcomes in patients with optic disc pit maculopathy: does peeling the ILM lead to better outcomes?

PURPOSE: Optic disc pits (ODPs) are rare congenital anomalies. Several patients develop optic disc pit maculopathy (ODP-M): visual impairment caused by intra- and/or subretinal fluid. Treatment mode remains controversial. This study was designed to investigate the effectiveness of pars plana vitrectomy (PPV) and gas tamponade with or without internal limiting membrane (ILM)-peeling in improving visual acuity and reducing subretinal fluid in ODP-M patients. METHODS: We retrospectively reviewed the charts of 16 patients who underwent surgery for ODP-M from 2002-2015. Six patients underwent PPV with gas tamponade (group 1); ten patients additionally received ILM-peeling (group 2). Pre- and postoperative visual acuity and central retinal thickness (CRT) were compared between groups, as well as retinal morphology and the number of secondary vitrectomies and complications. RESULTS: Median visual acuity improved by 2 ETDRS lines in both groups (p = 0.713, Mann-Whitney U test). Median CRT decreased by 426.5 µm and 460 µm (p = 0.931). One patient in group 1 underwent repeat vitrectomy for persistent retinoschisis. Three patients in group 2 required repeat vitrectomy: two to treat a macular hole, one for peripheral retinal holes with retinal detachment. CONCLUSION: In our cohort, PPV with gas tamponade proved to be an effective first-line treatment for ODP-M. Additional ILM-peeling did not give a significant benefit in this study.

Distribution of macular ganglion cell layer thickness in foveal hypoplasia: A new diagnostic criterion for ocular albinism.

BACKGROUND/AIMS: To analyse the distribution of macular ganglion cell layer thickness (GCLT) in patients with foveal hypoplasia (FH) with or without albinism to obtain new insights into visual pathway anomalies in albinos. METHODS: Patients with FH who presented at our institution between 2013 and 2018 were retrospectively drawn for analysis. Mean GCLT was calculated after automated segmentation of spectral domain-optical coherence tomography (SD-OCT) scans. Patients with FH due to albinism (n = 13, termed 'albinism FH') or other kinds (n = 10, termed 'non-albinism FH') were compared with control subjects (n = 15). The areas: fovea (central), parafovea (nasal I, temporal I) and perifovea (nasal II, temporal II) along the horizontal meridian were of particular interest. Primary endpoints of this study were the ratios (GCLT-I- and GCLT-II-Quotient) between the GCLT measured in the temporal I or II and nasal I or II areas. RESULTS: There was a significant difference between the GCLT-I-Quotient of healthy controls and albinism FH (p<0.001), as well as between non-albinism FH and albinism FH (p = 0.004). GCLT-II-Quotient showed significant differences between healthy controls and albinism FH (p<0.001) and between non-albinism FH and albinism FH (p = 0.006). The best measure for distinguishing between non-albinism FH and albinism FH was the calculation of GCLT-II-Quotient (area temporal II divided by area nasal II), indicating albinism at a cut-off of <0.7169. The estimated specificity and sensitivity for this cut-off were 84.6% and 100.0%, respectively. The estimated area under the curve (AUC) was 0.892 [95%CI: 0.743-1.000, p = 0.002]. CONCLUSION: Macular GCLT-distribution showed a characteristic temporal to central shift in patients with FH due to albinism. Calculation of the GCLT-II-Quotient at a cut-off of <0.7169 presents a new diagnostic criterion for identification of ocular albinism.

[What's New in Papilloedema, Pseudotumor Cerebri and Idiopathic Intracranial Hypertension]. / Stauungspapille, Pseudotumor cerebri und idiopathische intrakranielle Hypertension ­ Was gibt es Neues?

Several conditions share a cardinal feature on funduscopic examination: bilateral blurred optic disc margins. Pseudopapilledema (e.g., small hyperopic discs, tilted discs) and optic disc swelling can all be mistaken for papilloedema, which is caused by raised intracranial pressure. Diagnostic errors in papilloedema can lead to a delay of necessary treatments. This contribution will discuss the current progress in diagnosis and treatment of papilloedema and idiopathic intracranial hypertension. This clearly demonstrates that the new literature on pseudotumor cerebri syndrome and idiopathic intracranial hypertension has changed our understanding of its clinical picture during recent years and provides a key prerequisite for evidence-based recommendations on the management of affected patients. The optic nerve sheath meningocele as a rare differential diagnosis in that context will be discussed.

[Value of Optical Coherence Tomography Angiography in Neuroophthalmology]. / Stellenwert der optischen Kohärenztomografie-Angiografie bei neuroophthalmologischen Erkrankungen.

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.

Neuroprotection and neuroregeneration of retinal ganglion cells after intravitreal carbon monoxide release.

PURPOSE: Retinal ischemia induces apoptosis leading to neurodegeneration and vision impairment. Carbon monoxide (CO) in gaseous form showed cell-protective and anti-inflammatory effects after retinal ischemia-reperfusion-injury (IRI). These effects were also demonstrated for the intravenously administered CO-releasing molecule (CORM) ALF-186. This article summarizes the results of intravitreally released CO to assess its suitability as a neuroprotective and neuroregenerative agent. METHODS: Water-soluble CORM ALF-186 (25 µg), PBS, or inactivated ALF (iALF) (all 5 µl) were intravitreally applied into the left eyes of rats directly after retinal IRI for 1 h. Their right eyes remained unaffected and were used for comparison. Retinal tissue was harvested 24 h after intervention to analyze mRNA or protein expression of Caspase-3, pERK1/2, p38, HSP70/90, NF-kappaB, AIF-1 (allograft inflammatory factor), TNF-α, and GAP-43. Densities of fluorogold-prelabeled retinal ganglion cells (RGC) were examined in flat-mounted retinae seven days after IRI and were expressed as mean/mm2. The ability of RGC to regenerate their axon was evaluated two and seven days after IRI using retinal explants in laminin-1-coated cultures. Immunohistochemistry was used to analyze the different cell types growing out of the retinal explants. RESULTS: Compared to the RGC-density in the contralateral right eyes (2804±214 RGC/mm2; data are mean±SD), IRI+PBS injection resulted in a remarkable loss of RGC (1554±159 RGC/mm2), p<0.001. Intravitreally injected ALF-186 immediately after IRI provided RGC protection and reduced the extent of RGC-damage (IRI+PBS 1554±159 vs. IRI+ALF 2179±286, p<0.001). ALF-186 increased the IRI-mediated phosphorylation of MAP-kinase p38. Anti-apoptotic and anti-inflammatory effects were detectable as Caspase-3, NF-kappaB, TNF-α, and AIF-1 expression were significantly reduced after IRI+ALF in comparison to IRI+PBS or IRI+iALF. Gap-43 expression was significantly increased after IRI+ALF. iALF showed effects similar to PBS. The intrinsic regenerative potential of RGC-axons was induced to nearly identical levels after IRI and ALF or iALF-treatment under growth-permissive conditions, although RGC viability differed significantly in both groups. Intravitreal CO further increased the IRI-induced migration of GFAP-positive cells out of retinal explants and their transdifferentiation, which was detected by re-expression of beta-III tubulin and nestin. CONCLUSION: Intravitreal CORM ALF-186 protected RGC after IRI and stimulated their axons to regenerate in vitro. ALF conveyed anti-apoptotic, anti-inflammatory, and growth-associated signaling after IRI. CO's role in neuroregeneration and its effect on retinal glial cells needs further investigation.