Addressing corneal opacity after herpes zoster infection.

A 15-year-old boy was referred for corneal opacity evaluation. The patient had a previous herpes zoster virus (HZV) infection-varicella-zoster virus (VZV)-with ocular manifestation 1 year ago. After the infection, he developed a central corneal scar and decreased corrected distance visual acuity (CDVA) in the right eye. The slitlamp examination showed the right eye with central corneal opacity (involving anterior stroma), lacuna area between the haze, fluorescein negative, and no vascularization near the scar (Figure 1JOURNAL/jcrs/04.03/02158034-202406000-00019/figure1/v/2024-07-10T174224Z/r/image-tiff). The patient had been treated with oral valacyclovir and topical corticosteroids without any improvement of visual acuity or changes in opacity within the 1-year follow-up. His CDVA was 20/200 (-4.50 -0.75 × 25) in the right eye and counting fingers (-4.00) in the left eye. Intraocular pressure was 12 mm Hg in both eyes. Fundoscopy was normal in the right eye, but he had a macular scar in the left eye (diagnosed when he was 7 years). The left eye had no cornea signs. The patient has no comorbidity or previous surgeries. Considering this case, a corneal central scar in a 15-year-old boy, legally single eye only, and assuming it is an opacity in the anterior stroma, would you consider surgery for this patient? If so, which would you choose: Would you consider an excimer laser treatment of his ametropia while partially removing his opacity, a phototherapeutic keratectomy (PTK), or a PTK followed by a topography-guided treatment, femtosecond laser-assisted anterior lamellar keratoplasty (FALK), or deep anterior lamellar keratoplasty (DALK) or penetrating keratoplasty (depending on the scar depth)? Would you consider prophylactic acyclovir during and after surgery? Would you consider any other surgical step to prevent delayed corneal healing-persistent epithelial defect? Before the surgical approach, would you consider treating this patient with topical losartan (a transforming growth factor [TGF]-ß signaling inhibitor)? Would you first perform the surgery (which one) and then start the medication? Furthermore, if so, how long would you treat this patient? Would you consider treatment with another medication?

Longitudinal analysis of wound healing response post SMILE and LASIK surgery using proteomic profiling of tears.

Different types of refractive surgeries often exhibit differences in wound healing responses. The current study investigated post-operative tear protein profiles in subjects who underwent LASIK and SMILE to elucidate global changes to the proteomic profile during the period the patient cornea undergoes healing. In this study, 10 patients underwent LASIK and SMILE surgery with a contralateral paired eye design. Tear samples were collected using Schirmer's strips preoperatively, at 1 month, 3 months and 6 months postoperatively. Quantitative ITRAQ labeled proteomics was performed and the tear protein ratios were normalized to pre-operative protein levels for each subject. Whole proteomics identified 1345 proteins in tears from LASIK and 1584 proteins in SMILE across time points. About 67 proteins were common in LASIK and SMILE tears across all the time points. Wound healing responses were differentially regulated between two refractive surgeries (SMILE and LASIK). The proteins Ceruloplasmin, Clusterin, Serotransferrin were upregulated at 1 month and 3 months and downregulated at 6 months post operatively in LASIK surgery where as in SMILE these were downregulated. Galectin 3 binding protein showed upregulation at 1 month and the levels decreased at 3 months and 6 months postop in LASIK tears whereas the levels increased at 3 months and 6 months post-op in SMILE tears. The levels of proteins that protect from oxidative stress were higher in SMILE as compared to LASIK postoperatively. The extracellular matrix proteins showed an increase in expression at 6 months in SMILE tears and was stabilized at 6 months in LASIK tears post operatively. Different refractive surgeries induce distinct wound healing responses as identified in tears. This study has implications in targeting key proteins for improving the clinical outcome postrefractive surgery.

Quantitative and comparative analysis of thermography parameters in posterior scleritis, choroiditis, and controls.

PURPOSE: To compare various ocular thermography parameters in posterior scleritis (PS), choroiditis (choroidal granuloma [CG], Vogt-Koyanagi-Harada [VKH] syndrome), central serous chorioretinopathy (CSCR), and healthy controls. METHODS: This retrospective, observational, comparative study evaluated cases undergoing ocular thermography between April 2017 and October 2023. The study groups included cases of PS, CG, and VKH, while the control group comprised CSCR cases and healthy individuals. Various thermography parameters were assessed, which were as follows: Ocular surface temperature (OST), central corneal temperature (CCT), average scleral temperature (ST), nasal scleral temperature (nST), temperature difference between both the eyes (∆t), and difference between scleral and corneal temperatures (ST - CCT, nST - CCT). RESULTS: It was found that ∆t was significantly higher in the PS group compared to the CG ( P = 0.005), CSCR ( P = 0.0001), and control groups (dilated control: P =0.006, undilated control: P = 0.0001). ST - CCT and nST - CCT were significantly higher in the undilated control and CSCR groups and significantly lower in the PS group. ST - CCT and nST - CCT showed less difference in the affected eyes compared to contralateral healthy eyes of PS and CG cases. OST, CCT, ST, and nST displayed statistically insignificant differences across all groups. CONCLUSION: It is advisable to focus on temperature differences between the affected and healthy eyes, or the difference between the central corneal and scleral temperature of the affected eye, utilizing parameters such as ∆t, ST - CCT, and nST - CCT. These composite parameters offer a more effective approach than individual measurements like OST, CCT, ST, and nST. Thermography can serve as a screening tool to suspect and differentiate PS.

Inadvertent triple globe penetration during peribulbar anesthesia.

Inadvertent globe perforation following peribulbar anesthesia can lead to unpleasant experiences if not identified early and managed appropriately. We present the case of a 75-year-old female who came with decreased vision in the left eye (LE) following cataract surgery under peribulbar block. Her visual acuity in the right eye (RE) was 6/24 and LE was 6/75. Fundus examination of LE showed vitreous hemorrhage with localized subretinal hemorrhage along the inferotemporal arcade suggestive of globe perforation. Optical coherence tomography (OCT, Spectralis. Heidelberg imaging, Germany) scan across the perforation site showed subretinal hemorrhage and full-thickness retinal tear. On follow-up, two more focal points of retinal whitening were noted in the inferotemporal equatorial region. The patient was kept under close monitoring, and 4 weeks later, vision improved to 6/9 and barrage laser was done around the perforation sites. Serial OCT scans and close follow-up in iatrogenic globe perforation can result in good visual outcomes.

Spike sign - To predict the formation of big bubble in deep anterior lamellar keratoplasty in advanced keratoconus.

Lamellar surgeries have revolutionized our understanding and practice of keratoplasties. However, the learning curve in deep anterior lamellar keratoplasty (DALK) makes it daunting for novice surgeons. This paper describes a unique intraoperative sign - the radial "spike sign," which heralds the commencement of a big bubble in some cases of advanced keratoconus in eyes that have not undergone any previous surgery. The spike sign was noted during big bubble DALK surgery and was then retrospectively looked for in recorded DALK surgical videos and correlated with the formation of a big bubble. The movement of air after injection was classified into the direct formation of a big bubble, stromal emphysema with no big bubble, and emphysema with the spike sign followed by a big bubble. In total, 104 surgical videos of big bubble attempts were evaluated and classified as such. The spike sign helps reduce the number of unnecessary attempts at big bubble formation during DALK, thus improving surgical outcomes.

Hyperglycemia-induced miR182-5p drives glycolytic and angiogenic response in Proliferative Diabetic Retinopathy and RPE cells via depleting FoxO1.

PURPOSE: Diabetic Retinopathy (DR) is associated with metabolic dysfunction in cells such as retinal pigmented epithelium (RPE). Small molecular weight microRNAs can simultaneously regulate multiple gene products thus having pivotal roles in disease pathogenesis. Since miR182-5p is involved in regulating glycolysis and angiogenesis, two pathologic processes of DR, we investigated its status in DR eyes and in high glucose model in vitro. METHOD: ology: Total RNA was extracted from vitreous humor of PDR (n = 48) and macular hole (n = 22) subjects followed by quantification of miR182-5p and its target genes. ARPE-19 cells, cultured in DMEM under differential glucose conditions (5 mM and 25 mM) were used for metabolic and biochemical assays. Cells were transfected with miRNA182 mimic or antagomir to evaluate the gain and loss of function effects. RESULTS: PDR patient eyes had high levels of miR182-5p levels (p < 0.05). RPE cells under high glucose stress elevated miR182-5p expression with altered glycolytic pathway drivers such as HK2, PFKP and PKM2 over extended durations. Additionally, RPE cells under high glucose conditions exhibited reduced FoxO1 and enhanced Akt activation. RPE cells transfected with miR182-5p mimic phenocopied the enhanced basal and compensatory glycolytic rates observed under high glucose conditions with increased VEGF secretion. Conversely, inhibiting miR182-5p reduced Akt activation, glycolytic pathway proteins, and VEGF while stabilizing FoxO1. CONCLUSION: Glycolysis-associated proteins downstream of the FoxO1-Akt axis were regulated by miR182-5p. Further, miR182-5p increased expression of VEGFR2 and VEGF levels, likely via inhibition of ZNF24. Thus, the FoxO1-Akt-glycolysis/VEGF pathway driving metabolic dysfunction with concurrent angiogenic signaling in PDR may be potentially targeted for treatment via miR182-5p modulation.

Using adaptive optics to optimize the spherical aberration of eyes implanted with EDOF and enhanced monofocal intraocular lenses.

PURPOSE: To assess the effect of change in ocular spherical aberration (SA) with adaptive optics on visual acuity (VA) at different defocus after implantation of extended depth-of-focus (EDOF) and enhanced monofocal intraocular lenses (IOLs). SETTINGS: Narayana Nethralaya Eye Hospital, Bangalore, India. DESIGN: Prospective, longitudinal, observational. METHODS: 80 eyes (40 patients) that had cataract surgery were included in the study. 40 eyes were implanted with Eyhance EDOF IOLs and the remaining with Vivity EDOF IOLs. Baseline ocular aberrations were measured with a visual adaptive optics aberrometer, then the optimal SA was determined by increasing it in steps of -0.01 µm up to -0.1 µm until the maximum improvement in near distance VA was observed for a given eye. Then the defocus curve for each eye was measured after modifying the ocular SA by magnitude equal to optimal SA. RESULTS: Most of the eyes accepted a negative induced SA of -0.05 µm (Eyhance group: 67.6%; Vivity group, 45.2%). In the Eyhance group (dominant eyes), VA improved at -2 diopters (D) ( P < .02) only and degraded at 0 D, +0.5 D, and +1 D defocus ( P < .05). In the Vivity group, the VA remained unchanged at all defocus ( P > .05). In the Eyhance group (nondominant eyes), VA improved at -3.5 D defocus only and degraded at +1.5 D and +2 D defocus ( P < .05). In the Vivity group, VA improved at -2.5 D defocus ( P < .05) only. CONCLUSIONS: A negative induced SA of -0.05 µm in implanted eyes was optimal for a slight improvement in distance-corrected near and intermediate VA without any significant decrease in baseline distance-corrected VA.

Safety and Effectiveness of Smooth Incision Lenticular Keratomileusis (SILKTM) Using the ELITA(TM) Femtosecond Laser System for Correction of Myopic and Astigmatic Refractive Errors.

Purpose: To evaluate visual outcomes following the Smooth Incision Lenticular Keratomileusis (SILKTM) procedure for correction of myopic refractive errors with and without astigmatism, using the ELITATM Femtosecond Laser System. Patients and Methods: A prospective, multicenter, single-arm, open-label clinical study was conducted. Eighty-five myopic subjects (n = 170 eyes), aged 18 years or older, with manifest refractive spherical equivalent (MRSE) up to -12.00 D and astigmatism up to -6.00 D, were treated binocularly using the ELITA femtosecond laser and followed up for 6 months. Intended correction was emmetropia for all eyes. The primary outcome measures included post-operative uncorrected and corrected distance visual acuity (UDVA and CDVA). Secondary outcome measures included surgeon's rating for ease of lenticule extraction, predictability, safety, and stability. Results: A total of 170 eyes of 85 patients underwent SILK. Preoperative mean MRSE was -4.14 D ± 1.32 D (range -1.38 D to -8.88 D) and the mean cylinder was -0.77 D ± 0.62 D. Intraoperative surgeon ease of lenticule dissection was rated as grade 0 or 1 in 85.3% of eyes (no/only mild dissection needed). UDVA at 1 day, 1 week, 1 month, and 6 months was 20/20 or better in 65.9%, 85.4%, 91.5%, and 96% of eyes, respectively. No eyes lost any lines of CDVA at 6 months compared to the preoperative. The postoperative MRSE was stable over time, ranging from -0.34 D ± 0.24 D at 1 month to -0.33 D ± 0.23 D at 6 months. MRSE predictability (± 0.50 D) was 93.5% (129/138) at 3 months and 91.1% (113/124) at 6 months. No serious adverse events were noted. Conclusion: The SILK procedure with the ELITA Femtosecond Laser System is safe and effective for the treatment of myopic refractive errors with and without astigmatism. Fast visual recovery was demonstrated, with stability achieved by 3 months.

Simultaneous Topography-guided Custom Ablation With Corneal Cross-linking for Keratoconus: 10-Year Prospective Outcomes.

PURPOSE: To assess 10-year visual and tomographic outcomes of topography-guided custom ablation (T-CAT) with corneal cross-linking (CXL) in eyes with keratoconus. METHODS: T-CAT with CXL was performed in 600 eyes (522 patients). Based on the T-CAT ablation plan, the theoretical maximum ablation depth was 50 µm after epithelium removal. After ablation, accelerated corneal cross-linking (CXL) was performed in the central 8-mm zone (9 mW/cm2 for 10 minutes in "epi-off" mode). The visual acuity and tomography were assessed. RESULTS: There was significant improvement in uncorrected (P = .001) and corrected (P = .001) distance visual acuity after the procedure. Keratometry, root mean square lower order aberrations and higher order aberrations, defocus, coma 90°, and spherical aberration reduced significantly after surgery at 10 years of follow-up (P < .005). All Pentacam (Oculus Optikgerate GmbH) tomographic variables showed significant changes indicating regularization after T-CAT (P < .005). Flattening of greater than 5.00 diopters in maximum keratometry was noted in 6 eyes (1%). Two of 600 eyes progressed postoperatively and required repeat CXL. CONCLUSIONS: T-CAT plus CXL is a safe and effective technique even in the long term for regularizing the anterior corneal surface with significant visual improvement and reduction in higher order corneal aberrations. [J Refract Surg. 2023;39(11):759-766.].

Early detection and correlation of tear fluid inflammatory factors that influence angiogenesis in premature infants with and without retinopathy of prematurity.

Purpose: To measure the levels of inflammatory factors in tear fluid of pre-term infants with and without retinopathy of prematurity (ROP). Methods: The cross-sectional pilot study included 29 pre-term infants undergoing routine ROP screening. Pre-term infants were grouped as those without ROP (no ROP; n = 14) and with ROP (ROP; n = 15). Sterile Schirmer's strips were used to collect the tear fluid from pre-term infants. Inflammatory factors such as interleukin (IL)-6, IL-8, MCP1 (Monocyte Chemoattractant Protein 1; CCL2), RANTES (Regulated on Activation, Normal T Cell Expressed and Secreted; CCL5), and soluble L-selectin (sL-selectin) were measured by cytometric bead array using a flow cytometer. Results: Birth weight (BW) and gestation age (GA) were significantly (P < 0.05) lower in pre-term infants with ROP compared with those without ROP. Higher levels of RANTES (P < 0.05) and IL-8 (P = 0.09) were observed in the tear fluid of pre-term infants with ROP compared with those without ROP. Lower levels of tear fluid IL-6 (P = 0.14) and sL-selectin (P = 0.18) were measured in pre-term infants with ROP compared with those without ROP. IL-8 and RANTES were significantly (P < 0.05) higher in the tear fluid of pre-term infants with stage 3 ROP compared with those without ROP. Tear fluid RANTES level was observed to be inversely associated with GA and BW of pre-term infants with ROP and not in those without ROP. Furthermore, the area under the curve and odds ratio analysis demonstrated the relevance of RANTES/BW (AUC = 0.798; OR-7.2) and RANTES/MCP1 (AUC = 0.824; OR-6.8) ratios in ROP. Conclusions: Distinct changes were observed in the levels of tear inflammatory factors in ROP infants. The status of RANTES in ROP suggests its possible role in pathobiology and warrants further mechanistic studies to harness it in ROP screening and management.

Hemophagocytic Lymphohistiocytosis After Dengue Fever and Its Ocular Features.

This case report discusses a diagnosis of hemophagocytic lymphohistiocytosis in a man aged 40 years with a history of dengue fever.

Ocular manifestations following COVID-19 vaccination.

BACKGROUND: Immunologic and inflammatory adverse effects following vaccination against COVID-19 are being reported. While some reactions may develop denovo others concern its immunogenic effect in patients with pre-existing inflammatory conditions. METHODS: Retrospective consecutive patients diagnosed with ocular inflammatory manifestations within 8 weeks of receiving COVID-19 vaccination who presented to a tertiary eye care centre in South India. RESULTS: Ninety-eight eyes of 67 patients presenting with ocular inflammatory manifestations within 8 weeks following COVID-19 vaccination were studied. The mean age was 43 years (+/- 14.82; range 19-80 years). The most common presentations were anterior uveitis (n = 31, 31.7%), followed by panuveitis (n = 24, 24.5%). The mean time to onset of symptoms was 25 days (+/- 15.48; range 2-55 days) following a dose of vaccine. Among all patients, 39 (58.2%) had a previous history of ocular inflammation. Mean presenting visual acuity was 0.4 (0-4) logMAR units and mean final visual acuity was 0.2 (0-4) logMAR units. The causes for reduced vision included of cystoid macular edema (n=2, 2%), chorioretinal atrophy (n=2.2%), optic atrophy (n=1.1%), retinal vascular occlusion (n=1.1%) and acute retinal necrosis (n=1.1%). CONCLUSION: Infective and immunogenic adverse events should be watched out for after COVID-19 vaccination. It is difficult to establish causality for such manifestations, nevertheless, most of them were mild and had good final visual outcomes.

Correlation between tear levels of vascular endothelial growth factor and vitamin D at retinopathy of prematurity stages in preterm infants.

Deregulation of vascular endothelial growth factor (VEGF) levels leads to retinopathy of prematurity (ROP). Vitamin D (VIT-D) is known to regulate VEGF in an oxygen dependent manner. The purpose of this study was to correlate tear levels of VEGF and VIT-D with different ROP stages in preterm infants. In this prospective cross-sectional study, we enrolled 104 pre-term infants. They were grouped into: Group-1 (Classical ROP) and Group-2 (Aggressive ROP), which were further subdivided into Group-1A (progressing), Group-1B (regressing), Group-2A (pre-treatment), and Group-2B (post-treatment). Tear VEGF and VIT-D levels and their association with different ROP stages were assessed. Stage 1 and stage 2 had higher whereas stage 3 had lower VEGF levels in Group-1B compared to Group-1A. Stage 1 and stage 3 showed higher levels of VIT-D with no difference in stage 2 in Group-1B compared to Group-1A., Group-2B showed higher VEGF and lower VIT-D levels compared to Group-2A. Presence of a positive correlation at an early stage (stage 1) of ROP and a negative correlation at a more advanced stage (stage 3) of ROP with VIT-D and VEGF implies stage-specific distinct signaling crosstalk. These findings suggest that VIT-D supplementation may have the potential to modify the course and outcome of ROP.

Coronavirus disease 19 (COVID-19) and viral keratouveitis - unraveling the mystery.

To demonstrate viral proteins/inflammatory cytokines in a patient with unilateral keratouveitis. Retrospective case report. A 70-year-old Asian-Indian male presented with acute onset of blurring of vision in the left eye (OS) of 2 days duration. He had was coronavirus disease 2019 (COVID-19)-positive 3 months earlier. He had undergone cataract surgery/retinal laser photocoagulation in both the eyes. The corrected distance visual acuity (CDVA) (Snellen) in the right eye (RE) (OD) and left eye (LE) (OS) was 20/20 and 20/80, respectively. OS showed decreased corneal sensation, Descemet's folds, mild stromal edema, and fine and pigmented keratic precipitates with anterior chamber 1+ flare and 1+ cells. Fundus evaluation showed scattered laser marks in the OD and temporal sectoral laser marks in OS. He was diagnosed with viral keratouveitis in OS. Tear samples were collected on Schirmer's strips and tear wash for mass spectrometry and cytokines, which had 368 and 451 viral proteins in the RE and LE, respectively, using nano liquid chromatography-mass spectrometry, which were more than controls. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and varicella zoster virus proteins were detected. Cytokine analysis using flow cytometer analysis showed higher inflammation in OS as compared to OD. The patient was treated with oral acyclovir and topical steroids and resulted in resolution of his keratouveitis. SARS-CoV-2 proteins were present in the tear sample 3 months after COVID-19. The presence of viral proteins does not indicate causality.

Comparison of intraocular lens power prediction accuracy of formulas in American Society of Cataract and Refractive Surgery post-refractive surgery calculator in eyes with prior radial keratotomy.

Purpose: To evaluate the accuracy of intraocular lens (IOL) power prediction of the formulas available on the American Society of Cataract and Refractive Surgery (ASCRS) post-refractive calculator in eyes with prior radial keratotomy (RK) for myopia. Methods: This retrospective study included 25 eyes of 18 patients whose status was post-RK for treatment of myopia, which had undergone cataract extraction with IOL implantation. Prediction error was calculated as the difference between implanted IOL power and predicted power by various formulae available on ASCRS post-refractive calculator. The formulas compared were Humphrey Atlas method, IOLMaster/Lenstar method, Barrett True-K no-history formula, ASCRS Average power, and ASCRS Maximum power on ASCRS post-refractive calculator. Results: Median absolute errors were the least for Barrett True-K and ASCRS Maximum power, that is, 0.56 (0.25, 1.04) and 0.56 (0.25, 1.06) D, respectively, and that of Atlas method was 1.60 (0.85, 2.28) D. Median arithmetic errors were positive for Atlas, Barrett True-K, ASCRS Average (0.86 [-0.17, 1.61], 0.14 [-0.22 to 0.54], and 0.23 [-0.054, 0.76] D, respectively) and negative for IOLMaster/Lenstar method and ASCRS Maximum power (-0.02 [-0.46 to 0.38] and - 0.48 [-1.06 to - 0.22] D, respectively). Multiple comparison analysis of Friedman's test revealed that Atlas formula was significantly different from IOLMaster/Lenstar, Barrett True-K, and ASCRS Maximum power; ASCRS Maximum power was significantly different from all others (P < 0.00001). Conclusion: In post-RK eyes, Barrett True-K no-history formula and ASCRS Maximum power given by the ASCRS calculator were more accurate than other available formulas, with ASCRS Maximum leading to more myopic outcomes when compared to others.

Depleted hexokinase1 and lack of AMPKα activation favor OXPHOS-dependent energetics in retinoblastoma tumors.

Lack of retinoblastoma (Rb) protein causes aggressive intraocular retinal tumors in children. Recently, Rb tumors have been shown to have a distinctly altered metabolic phenotype, such as reduced expression of glycolytic pathway proteins alongside altered pyruvate and fatty acid levels. In this study, we demonstrate that loss of hexokinase 1(HK1) in tumor cells rewires their metabolism allowing enhanced oxidative phosphorylation-dependent energy production. We show that rescuing HK1 or retinoblastoma protein 1 (RB1) in these Rb cells reduced cancer hallmarks such as proliferation, invasion, and spheroid formation and increased their sensitivity to chemotherapy drugs. Induction of HK1 was accompanied by a metabolic shift of the cells to glycolysis and a reduction in mitochondrial mass. Cytoplasmic HK1 bound Liver Kinase B1 and phosphorylated AMP-activated kinase-α (AMPKα Thr172), thereby reducing mitochondria-dependent energy production. We validated these findings in tumor samples from Rb patients compared to age-matched healthy retinae. HK1 or RB1 expression in Rb-/- cells led to a reduction in their respiratory capacity and glycolytic proton flux. HK1 overexpression reduced tumor burden in an intraocular tumor xenograft model. AMPKα activation by AICAR also enhanced the tumoricidal effects of the chemotherapeutic drug topotecan in vivo. Therefore, enhancing HK1 or AMPKα activity can reprogram cancer metabolism and sensitize Rb tumors to lower doses of existing treatments, a potential therapeutic modality for Rb.

Choroidal Involvement and Chronic Macular Edema in Acute Retinal Necrosis: A Novel Finding and a Novel Treatment.

Acute retinal necrosis (ARN) as the term suggests is recognized as necrotic inflammation of retina, in contrast to toxoplasma retinochoroiditis where involvement of choroid can be appreciated as choroidal thickening on optical coherence tomography scan during active stage. Secondly, sequelae of ARN, such as chronic anterior uveitis and cystoid macular edema, could be challenging to manage as steroid use in various forms poses a risk of virus reactivation. We present a case of ARN caused by varicella zoster virus with an initial confusing clinical picture with toxoplasma retinochoroiditis, documented with choroidal involvement. The patient also developed a chronic anterior uveitis with macular edema after resolution of ARN which was treated with topical interferon (IFN) alfa 2b therapy with successful outcome. This report supports the recently described choroidal involvement in ARN and suggests topical IFN as a novel treatment in management of chronic macular edema post ARN.

Corneal Regeneration Using Gene Therapy Approaches.

One of the most remarkable advancements in medical treatments of corneal diseases in recent decades has been corneal transplantation. However, corneal transplants, including lamellar strategies, have their own set of challenges, such as graft rejection, delayed graft failure, shortage of donor corneas, repeated treatments, and post-surgical complications. Corneal defects and diseases are one of the leading causes of blindness globally; therefore, there is a need for gene-based interventions that may mitigate some of these challenges and help reduce the burden of blindness. Corneas being immune-advantaged, uniquely avascular, and transparent is ideal for gene therapy approaches. Well-established corneal surgical techniques as well as their ease of accessibility for examination and manipulation makes corneas suitable for in vivo and ex vivo gene therapy. In this review, we focus on the most recent advances in the area of corneal regeneration using gene therapy and on the strategies involved in the development of such therapies. We also discuss the challenges and potential of gene therapy for the treatment of corneal diseases. Additionally, we discuss the translational aspects of gene therapy, including different types of vectors, particularly focusing on recombinant AAV that may help advance targeted therapeutics for corneal defects and diseases.

Efficacy of customized corneal crosslinking versus standard corneal crosslinking in patients with progressive keratoconus (C-CROSS study): study protocol for a randomized controlled trial.

BACKGROUND: Keratoconus is a degenerative disorder of the cornea leading to a protrusion and thinning with loss of visual acuity. The only treatment to halt the progression is corneal crosslinking (CXL), which uses riboflavin and UV-A light to stiffen the cornea. Recent ultra-structural examinations show that the disease is regional and does not affect the entire cornea. Treating only the affected zone with CXL could be as good as the standard CXL, that treats the entire cornea. METHODS: We set up a multicentre non-inferiority randomized controlled clinical trial comparing standard CXL (sCXL) and customized CXL (cCXL). Patients between 16 and 45 years old with progressive keratoconus were included. Progression is based on one or more of the following changes within 12 months: 1 dioptre (D) increase in keratometry (Kmax, K1, K2); or 10% decrease of corneal thickness; or 1 D increase in myopia or refractive astigmatism, requiring corneal crosslinking. DISCUSSION: The goal of this study is to evaluate whether the effectiveness of cCXL is non-inferior to sCXL in terms of flattening of the cornea and halting keratoconus progression. Treating only the affected zone could be beneficial for minimalizing the risk of damaging surrounding tissues and faster wound healing. Recent non-randomized studies suggest that a customized crosslinking protocol based on the tomography of the patient's cornea may stop the progression of keratoconus and result in flattening of the cornea. TRIAL REGISTRATION: This study was prospectively registered at ClinicalTrials.gov on August 31st, 2020, the identifier of the study is NCT04532788.

Choroidal lesions in varicella zoster virus uveitis.

Purpose: To evaluate choroidal lesions with spectral domain optical coherence tomography (SD-OCT) scan in varicella zoster virus (VZV) uveitis. Methods: VZV-uveitis cases which underwent OCT scan for choroidal lesions were studied. SD-OCT scan passing through these lesions was studied in detail. Subfoveal choroidal thickness (SFCT) during active and resolved stages was studied. Angiogaphic features were studied where available. Results: Thirteen out of 15 cases had same-sided herpes zoster ophthalmicus skin rashes. All except three patients had old or active kerato-uveitis. All eyes demonstrated clear vitreous and a single or multiple hypopigmented orangish-yellow choroidal lesions. The number of lesions remained unchanged during the follow-up on clinical examination. SD-OCT over lesions (n = 11) showed choroidal thinning (n = 5), hyporeflective choroidal elevation during active inflammation (n = 3), transmission effects (n = 4), and ellipsoid zone disruption (n = 7). The mean change in SFCT (n = 9) after resolution of the inflammation was 26.3 µm (range: 3-90 µm). Fundus fluorescein angiography showed iso-fluorescence over lesions in all (n = 5), but indocyanine green angiography (n = 3) showed hypofluorescence at lesions. Mean follow-up was 1.38 years (range: 3 months-7 years). De-novo appearance of choroidal lesion during the first relapse of VZV-uveitis was captured in one case. Conclusion: VZV-uveitis can cause focal or multifocal hypopigmented choroidal lesions with thickening or scarring of choroidal tissue, depending on the disease activity.