Atopic Dermatitis Leading to Blindness: A Frequently Forgotten Sequelae.

A 12-year-old boy with underlying severeand poorly controlled atopic dermatitis (AD) associated with atopic conjunctivitis and rhinitis presented with a right painless blurring of vision for two weeks. On examination, his right eye visual acuity was 1/60,with grade 1 relative afferent pupillary defect (RAPD). Anterior segment examination revealed anterior uveitis with dense posterior subcapsular cataract and hazy fundus view. B-scan ultrasound suggested a shallow total retinal detachment. Intraoperatively, a large retinal dialysis was found. This paper highlights the need for a high index of suspicion of retinal dialysis in a child with underlying AD and the importance of good control of this systemic condition to prevent ocular morbidity.

The Importance of Posterior Hyaloid Removal in a Case of Vitrectomy for Floaters in High Myopia.

A 61-year-old Malaysian Chinese man who has high myopia complained of both eye floaters. Spectral-domain optical coherence tomography (SD-OCT) of the macula showed bilateral posterior staphyloma with right eye (RE) foveoschisis without macula detachment, which had been stable for a seven-year follow-up. When bilateral YAG laser vitreolysis could not alleviate his symptoms, he underwent pars plana vitrectomy with the inducement of posterior vitreous detachment, first in the left eye, followed by the RE one month later. The best-corrected visual acuity for both eyes was 6/6, N5 two months postoperatively, and he was asymptomatic for floaters. However, six months postoperatively, he complained of metamorphopsia and worsening RE vision. Repeat OCT showed worsening of the foveoschisis bilaterally with left foveal detachment. The patient had to undergo a repeat vitrectomy with peeling of the internal limiting membrane (ILM) in bilateral eyes, which successfully restored his foveal architecture and alleviated his symptoms. This article highlights theimportance of preoperative OCT assessment of the fovea in patients undergoing vitrectomy for floaters, as staining and complete removal of posterior hyaloid with ILM peeling during vitrectomy may mitigate the progression of foveoschisis after core vitrectomy for floaters in myopic patients.

Myelin oligodendrocyte glycoprotein antibody-associated optic neuritis in a post-COVID-19 infection patient.

PURPOSE: SARS-CoV-2 viral infection affects multiple systems including the respiratory, gastrointestinal, neurological, cardiac, and ophthalmic systems. We report a case of myelin oligodendrocyte glycoprotein (MOG) related optic neuritis in a SARS-CoV-2 (COVID-19) patient. METHODS: Case report. RESULTS: A 36-year-old Malay gentleman with underlying hypertension presented with the first episode of bilateral progressively worsening blurred vision for 1 week associated with retrobulbar pain. There were no other neurological symptoms. He had fever a week before the eye symptoms and tested positive for COVID-19. He received COVID-19 booster vaccine a month before the disease onset. On examination, his vision was hand motion on right eye and 6/18 on left eye. Relative afferent pupillary defect (RAPD) was positive on right eye with abnormal optic nerve function tests. Anterior segments were unremarkable. Fundus examination showed bilateral optic disc swelling. MRI revealed multifocal hyperintense subcortical white matter lesions. Optic nerves appeared normal with no enhancement seen. Blood investigation showed a positive serum MOG antibody. Intravenous methylprednisolone was commenced followed by oral prednisolone after which his vision and ocular symptoms markedly improved. The oral prednisolone was tapered alongside addition of azathioprine. At 1 month, the disease was stable with no recurrence. CONCLUSION: While optic neuritis has been associated with both COVID-19 infection and vaccination, MOG IgG antibody-mediated optic neuritis is also a possible manifestation. This type of optic neuritis associated with COVID-19 infection does not show a similar pattern of frequent recurrences as seen in non-COVID-19 related optic neuritis.

Corrigendum: Transplanted Erythropoietin-Expressing Mesenchymal Stem Cells Promote Pro-survival Gene Expression and Protect Photoreceptors From Sodium Iodate-Induced Cytotoxicity in a Retinal Degeneration Model.

[This corrects the article DOI: 10.3389/fcell.2021.652017.].

Transplanted Erythropoietin-Expressing Mesenchymal Stem Cells Promote Pro-survival Gene Expression and Protect Photoreceptors From Sodium Iodate-Induced Cytotoxicity in a Retinal Degeneration Model.

Mesenchymal stem cells (MSC) are highly regarded as a potential treatment for retinal degenerative disorders like retinitis pigmentosa and age-related macular degeneration. However, donor cell heterogeneity and inconsistent protocols for transplantation have led to varied outcomes in clinical trials. We previously showed that genetically-modifying MSCs to express erythropoietin (MSCEPO) improved its regenerative capabilities in vitro. Hence, in this study, we sought to prove its potential in vivo by transplanting MSCsEPO in a rat retinal degeneration model and analyzing its retinal transcriptome using RNA-Seq. Firstly, MSCsEPO were cultured and expanded before being intravitreally transplanted into the sodium iodate-induced model. After the procedure, electroretinography (ERG) was performed bi-weekly for 30 days. Histological analyses were performed after the ERG assessment. The retina was then harvested for RNA extraction. After mRNA-enrichment and library preparation, paired-end RNA-Seq was performed. Salmon and DESeq2 were used to process the output files. The generated dataset was then analyzed using over-representation (ORA), functional enrichment (GSEA), and pathway topology analysis tools (SPIA) to identify enrichment of key pathways in the experimental groups. The results showed that the MSCEPO-treated group had detectable ERG waves (P <0.05), which were indicative of successful phototransduction. The stem cells were also successfully detected by immunohistochemistry 30 days after intravitreal transplantation. An initial over-representation analysis revealed a snapshot of immune-related pathways in all the groups but was mainly overexpressed in the MSC group. A subsequent GSEA and SPIA analysis later revealed enrichment in a large number of biological processes including phototransduction, regeneration, and cell death (Padj <0.05). Based on these pathways, a set of pro-survival gene expressions were extracted and tabulated. This study provided an in-depth transcriptomic analysis on the MSCEPO-treated retinal degeneration model as well as a profile of pro-survival genes that can be used as candidates for further genetic enhancement studies on stem cells.

Human Dental Pulp Stem Cells (DPSCs) Therapy in Rescuing Photoreceptors and Establishing a Sodium Iodate-Induced Retinal Degeneration Rat Model.

BACKGROUND: Different methods have been used to inject stem cells into the eye for research. We previously explored the intravitreal route. Here, we investigate the efficacy of intravenous and subretinal-transplanted human dental pulp stem cells (DPSCs) in rescuing the photoreceptors of a sodium iodate-induced retinal degeneration model. METHODS: Three groups of Sprague Dawley rats were used: intervention, vehicle group and negative control groups (n = 6 in each). Intravenous injection of 60 mg/kg sodium iodate (day 0) induced retinal degeneration. On day 4 post-injection of sodium iodate, the rats in the intervention group received intravenous DPSC and subretinal DPSC in the right eye; rats in the vehicle group received subretinal Hank's balance salt solution and intravenous normal saline; while negative control group received nothing. Electroretinogram (ERG) was performed to assess the retinal function at day 0 (baseline), day 4, day 11, day 18, day 26, and day 32. By the end of the study at day 32, the rats were euthanized, and both their enucleated eyes were sent for histology. RESULTS: No significant difference in maximal ERG a-wave (p = 0.107) and b-wave, (p = 0.153) amplitude was seen amongst the experimental groups. However, photopic 30 Hz flicker amplitude of the study eye showed significant differences in the 3 groups (p = 0.032). Within the intervention group, there was an improvement in 30 Hz flicker ERG response of all 6 treated right eyes, which was injected with subretinal DPSC; while the 30 Hz flicker ERG of the non-treated left eyes remained flat. Histology showed improved outer nuclear layer thickness in intervention group; however, findings were not significant compared to the negative and vehicle groups. CONCLUSION: Combination of subretinal and intravenous injection of DPSCs may have potential to rescue cone function from a NaIO3-induced retinal injury model.

Looking into dental pulp stem cells in the therapy of photoreceptors and retinal degenerative disorders.

Blindness and vision impairment are caused by irremediable retinal degeneration in affected individuals worldwide. Cell therapy for a retinal replacement can potentially rescue their vision, specifically for those who lost the light sensing photoreceptors in the eye. As such, well-characterized retinal cells are required for the replacement purposes. Stem cell-based therapy in photoreceptor and retinal pigment epithelium transplantation is well received, however, the drawbacks of retinal transplantation is the limited clinical protocols development, insufficient number of transplanted cells for recovery, the selection of potential stem cell sources that can be differentiated into the target cells, and the ability of cells to migrate to the host tissue. Dental pulp stem cells (DPSC) belong to a subset of mesenchymal stem cells, and are recently being studied due to its high capability of differentiating into cells of the neuronal lineage. In this review, we look into the potential uses of DPSC in treating retinal degeneration, and also the current data supporting its application.

Dental pulp stem cells therapy overcome photoreceptor cell death and protects the retina in a rat model of sodium iodate-induced retinal degeneration.

Blindness and vision loss contribute to irreversible retinal degeneration, and cellular therapy for retinal cell replacement has the potential to treat individuals who have lost light sensitive photoreceptors in the retina. Retinal cells are well characterized in function, and are a subject of interest in cellular replacement therapy of photoreceptors and the retinal pigment epithelium. However, retinal cell transplantation is limited by various factors, including the choice of potential stem cell source that can show variability in plasticity as well as host tissue integration. Dental pulp is one such source that contains an abundance of stem cells. In this study we used dental pulp-derived mesenchymal stem cells (DPSCs) to mitigate sodium iodate (NaIO3) insult in a rat model of retinal degeneration. Sprague-Dawley rats were first given an intravitreal injection of 3 × 105 DPSCs as well as a single systemic administration of NaIO3 (40 mg/kg). Electroretinography (ERG) was performed for the next two months and was followed-up by histological analysis. The ERG recordings showed protection of DPSC-treated retinas within 4 weeks, which was statistically significant (* P ≤ .05) compared to the control. Retinal thickness of the control was also found to be thinner (*** P ≤ .001). The DPSCs were found integrated in the photoreceptor layer through immunohistochemical staining. Our findings showed that DPSCs have the potential to moderate retinal degeneration. In conclusion, DPSCs are a potential source of stem cells in the field of eye stem cell therapy due to its protective effects against retinal degeneration.

Retinal degeneration rat model: A study on the structural and functional changes in the retina following injection of sodium iodate.

Retinal disorders account for a large proportion of ocular disorders that can lead to visual impairment or blindness, and yet our limited knowledge in the pathogenesis and choice of appropriate animal models for new treatment modalities may contribute to ineffective therapies. Although genetic in vivo models are favored, the variable expressivity and penetrance of these heterogeneous disorders can cause difficulties in assessing potential treatments against retinal degeneration. Hence, an attractive alternative is to develop a chemically-induced model that is both cost-friendly and standardizable. Sodium iodate is an oxidative chemical that is used to simulate late stage retinitis pigmentosa and age-related macular degeneration. In this study, retinal degeneration was induced through systemic administration of sodium iodate (NaIO3) at varying doses up to 80 mg/kg in Sprague-Dawley rats. An analysis on the visual response of the rats by electroretinography (ERG) showed a decrease in photoreceptor function with NaIO3 administration at a dose of 40 mg/kg or greater. The results correlated with the TUNEL assay, which revealed signs of DNA damage throughout the retina. Histomorphological analysis also revealed extensive structural lesions throughout the outer retina and parts of the inner retina. Our results provided a detailed view of NaIO3-induced retinal degeneration, and showed that the administration of 40 mg/kg NaIO3 was sufficient to generate disturbances in retinal function. The pathological findings in this model reveal a degenerating retina, and can be further utilized to develop effective therapies for RPE, photoreceptor, and bipolar cell regeneration.

Case series of children with steroid-Induced glaucoma

@#Steroid-induced glaucoma is the most serious complication of the injudicious use of steroids, particularly among children affected by allergic conjunctivitis. This condition is steroid-dependent, and children are commonly being prescribed topical anti-inflammatories, including topical steroids, by general practitioners. Furthermore, topical steroids are also available over the counter, and this availability contributes to overuse without proper monitoring by an ophthalmologist. We present a series of five cases illustrating the devastating effect of unmonitored, long-term use of steroids among children for vernal keratoconjunctivitis. The medications were prescribed initially by general ophthalmologists and were continually bought over the counter by parents. At the presentation to our center, these patients were already compromised visually, exhibiting glaucomatous optic disc changes and high intraocular pressure. The series highlights the optic nerve damage resulting in irreversible visual compromises among children on long-term, topical steroids and the importance of regular monitoring with a low threshold for ophthalmologist referral.