Incidence of COVID-19 Vaccination-Related Uveitis and Effects of Booster Dose in a Tertiary Uveitis Referral Center.

Background: We report vaccine and booster-related uveitis in Singapore, a country with high vaccination and booster rates to highlight the differences and potential role of prophylactic treatment for sight-threatening infectious uveitis. Methods: Clinical data extracted from the de-identified uveitis database in Singapore National Eye Center. Six patients (eight eyes) developed uveitis within 14 days after undergoing COVID-19 vaccination (primary and/or booster). Results: All patients received two doses of COVID-19 vaccination, and 1.39% (6/431) developed COVID-19 vaccine-related uveitis. Fifty-percent% (3/6) with non-infectious anterior uveitis (NIAU) presented with a non-granulomatous anterior uveitis (AU). The remaining (3/6) presenting with a granulomatous AU were diagnosed with reactivation of cytomegalovirus, varicella-zoster virus and toxoplasma chorioretinitis, respectively. All the patients responded to definitive treatment specific to their diagnosis. The mean visual acuity at presentation was 0.36 ± 0.20 logMAR and improved to 0.75 ± 0.09 (p = 0.009). Mean time from vaccination to uveitis was 9.7 (range: 3-14) days. All patients developed uveitis after second vaccination dose. 16.67% (1/6) patients had a recurrence after the third booster dose. None of the three patients with infectious uveitis developed recurrence but had received maintenance therapy up to or during the booster. Conclusion: Uveitis after COVID-19 vaccination is uncommon. In our series, a higher rate of reactivations of latent infections was seen. With definitive treatment, all cases were self-limited without systemic sequelae. Prophylactic treatment during booster vaccine may prevent reactivation of sight-threatening infections and reduce morbidity although risk-benefits should be considered for individual patients given the low rate of occurrence.

The Management of Ocular Surface Squamous Neoplasia (OSSN).

The rise of primary topical monotherapy with chemotherapeutic drugs and immunomodulatory agents represents an increasing recognition of the medical management of ocular surface squamous neoplasia (OSSN), which may replace surgery as the standard of care in the future. Currently, there is no consensus regarding the best way to manage OSSN with no existing guidelines to date. This paper seeks to evaluate evidence surrounding available treatment modalities and proposes an approach to management. The approach will guide ophthalmologists in selecting the most appropriate treatment regime based on patient and disease factors to minimize treatment related morbidity and improve OSSN control. Further work can be done to validate this algorithm and to develop formal guidelines to direct the management of OSSN.

Corneal Inlay Damage After Cosmetic Laser Treatment of the Eyelid With Long-Pulsed Nd:YAG Laser.

Importance: Protective eyewear or corneal shields are recommended during cosmetic facial laser treatment. Objective: To describe the occurrence of corneal inlay damage following treatment to the eyelids and face with an Nd:YAG laser. Design, Setting, and Participants: This observational case report includes a single incident case cared for at a tertiary care center. A 58-year-old man who had undergone bilateral uncomplicated myopic laser in situ keratomileusis surgery in 2003 and corneal inlay implant in the nondominant left eye in 2013 experienced decreased visual acuity (VA) and pain in the left eye after the application of 2 passes of the Nd:YAG laser to his face and both eyelids for facial tightening. At presentation, the uncorrected VA was counting fingers OS and 20/20 OD. Slitlamp biomicroscopy showed a corneal epithelial defect overlying a deformed corneal inlay, peripheral scattered pigmentary deposits, corneal haze, and brown discoloration of the lamellar pocket of the inlay. He underwent explant of the inlay and debridement 48 hours later because of deteriorating VA and increasing corneal haze. Exposure: Application of long-pulsed Nd:YAG laser at 1064 nm to the middle one-third of both upper eyelids and the periorbital region in a man with a corneal inlay implant. Corneal shields were not worn during the procedure. The peak penetration depth of this laser system is approximately 4 mm. The mean (SD) thickness of the upper eyelid in Asian eyes is 1.127 (0.238) mm. Main Outcomes and Measures: Improvement of corneal inlay damage. Results: In this 58-year-old man, 3 months after the inlay explant, the intrastromal discoloration had resolved. There was still residual corneal haze, but the patient was able to achieve a best-corrected VA of 20/25 OS for distance and J3 (Snellen equivalent, 20/30) OS for near. Conclusions and Relevance: Although the exact cause and effect cannot be determined from a single case, our findings suggest that a history of corneal inlay implant should be asked about prior to any long-pulsed Nd:YAG laser treatment to the periorbital skin and eyelids. Furthermore, these findings suggest that laser treatment to the eyelids should be avoided and that protective eyewear or corneal shields are recommended during cosmetic facial laser treatment in all patients.

Corneal Inlays for Presbyopia Explanted Due to Corneal Haze.

PURPOSE: To present 3 patients who required explantation of KAMRA inlays (AcuFocus, Inc., Irvine, CA) due to visual symptoms caused by postoperative corneal haze. METHODS: Case series. RESULTS: All patients had good near and distance vision immediately following implantation. They developed visual symptoms 3 to 6 years later. All patients reported a decline in distance vision. Two patients had hyperopic shift with flattening of the central cornea. Six months following explantation, all patients reported improvement in visual symptoms. A reversal of hyperopic shift was also observed, with improvement in corneal profiles on topography. Histopathology of the explanted inlays showed thin, acellular collagenous fibrotic membranes over the inlays with occasional chronic inflammatory cells. CONCLUSIONS: It is important for health care professionals to be made aware of this reversible complication following KAMRA inlay implantation. Long-term monitoring is recommended. [J Refract Surg. 2018;34(5):357-360.].

Primary angle closure glaucoma (PACG) susceptibility gene PLEKHA7 encodes a novel Rac1/Cdc42 GAP that modulates cell migration and blood-aqueous barrier function.

PLEKHA7, a gene recently associated with primary angle closure glaucoma (PACG), encodes an apical junctional protein expressed in components of the blood aqueous barrier (BAB). We found that PLEKHA7 is down-regulated in lens epithelial cells and in iris tissue of PACG patients. PLEKHA7 expression also correlated with the C risk allele of the sentinel SNP rs11024102 with the risk allele carrier groups having significantly reduced PLEKHA7 levels compared to non-risk allele carriers. Silencing of PLEKHA7 in human immortalized non-pigmented ciliary epithelium (h-iNPCE) and primary trabecular meshwork cells, which are intimately linked to BAB and aqueous humor outflow respectively, affected actin cytoskeleton organization. PLEKHA7 specifically interacts with GTP-bound Rac1 and Cdc42, but not RhoA, and the activation status of the two small GTPases is linked to PLEKHA7 expression levels. PLEKHA7 stimulates Rac1 and Cdc42 GTP hydrolysis, without affecting nucleotide exchange, identifying PLEKHA7 as a novel Rac1/Cdc42 GAP. Consistent with the regulatory role of Rac1 and Cdc42 in maintaining the tight junction permeability, silencing of PLEKHA7 compromises the paracellular barrier between h-iNPCE cells. Thus, downregulation of PLEKHA7 in PACG may affect BAB integrity and aqueous humor outflow via its Rac1/Cdc42 GAP activity, thereby contributing to disease etiology.

Serum IgG2 and tissue IgG2 plasma cell elevation in orbital IgG4-related disease (IgG4-RD): Potential use in IgG4-RD assessment.

AIMS: To determine the role of serum and tissue IgG2 in orbital biopsies with the histological features of IgG4-related disease (IgG4-RD) in comparison with non-IgG4-related orbital inflammatory disorders (OID), including autoimmune disorders. METHODS: This is an international (Sheffield, UK, and Singapore) collaborative, retrospective case review of 69 patients (38 from Singapore National Eye Centre and 31 from Royal Hallamshire Hospital, Sheffield) with orbital inflammatory biopsies between 2002 and 2016. Clinical information and histology were reviewed and cases were classified into three groups: Group 1: IgG4-RD orbital inflammation (n=43); Group 2: idiopathic OID (n=12) and Group 3: autoimmune OID (n=14). Serum IgG1, IgG2, IgG3 and IgG4 levels were collated where available and immunohistochemistry (IHC) for tissue IgG2 plasma cells was performed. RESULTS: Dual IHC showed IgG2 plasma cells as a distinct population from IgG4 plasma cells. Significant (twofold) serum IgG2 elevation was noted among IgG4-RD (group 1), idiopathic (group 2) and autoimmune OID (group 3). Similarly, significant elevation of tissue IgG2 plasma cells was also seen among IgG4-RD (group 1), idiopathic and autoimmune OID (groups 2 and 3). CONCLUSIONS: Significant elevations of serum IgG2 and tissue IgG2 plasma cells are present in orbital IgG4-RD in comparison with non-IgG4 orbital inflammation (idiopathic and autoimmune OID), suggesting that IgG2 may play a role in IgG4-RD. A serum IgG2 cut-off >5.3 g/L was found to be 80% sensitive and 91.7% specific for orbital IgG4-RD, with an accuracy of 0.90. Tissue IgG2 and IgG4 subclass reporting may provide additional insight regarding the 'IgG4-RD' pathogenesis.

Clinical Features and Treatment Outcomes of Orbital Inflammatory Disease in Singapore: A 10-Year Clinicopathologic Review.

PURPOSE: 1) To assess the clinical profile and treatment outcomes of orbital inflammatory disease in the local population, and 2) classify patients using current histopathological criteria. METHODS: Ten-year retrospective clinicopathologic review of patients diagnosed with orbital inflammatory disease who underwent tissue biopsy from January 2001 to December 2011 at a tertiary referral centre in Singapore. Data collection included patient demographics, clinical presentation, investigations, systemic disease, histopathology review, clinical classification, medical and surgical management, response to treatment and recurrence rates. RESULTS: The study comprised 70 patients. Thirty-seven (52.9%) had nonspecific inflammation distributed as follows: lacrimal (n = 23), diffuse (n = 5), anterior (n = 5), myositic (n = 4). Thirty-three (47.1%) had specific inflammation of the following subtypes: idiopathic sclerosing inflammation (n = 9), granulomatous disorders (n = 8), transitional lesions (n = 5), vasculitis (n = 4), and others (n = 7). A total of 76.8% of patients received oral prednisolone, with a median duration of three months. Response to treatment was good in 71.9% of patients. Recurrence occurred in 22 (32.8%) patients at a mean interval of 20 months after completion of treatment, and was higher in myositic and vasculitic subtypes. There was no significant correlation between duration of treatment and recurrence. CONCLUSIONS: This study has re-emphasized the importance and utility of orbital biopsy and histopathologic typing for optimal management of orbital inflammatory disease. It has also improved the knowledge of the rate and response to treatment of its various subtypes.

Histological features of Cytomegalovirus-related corneal graft infections, its associated features and clinical significance.

AIM: To describe the histological features of ITALIC! Cytomegalovirus (CMV)-related corneal graft infections, its associated features and clinical significance. METHODS: This was a retrospective histological study of 48 consecutive cases of failed repeat penetrating keratoplasty cases with a clinical diagnosis of allograft rejection from 2011 to 2013. CMV infection was confirmed with CMV antibody immunohistochemistry (IHC) and electron microscopy. Additional CD163 and CD68 IHCs for macrophages were also performed. Clinical data and previous graft histology were then reviewed. RESULTS: Mean incidence of CMV infection in corneal graft rejection buttons was 6.3% per year. 3/48 graft buttons were CMV antibody positive. Histological features of CMV graft infection include: (1) stromal keratocytes with cytopathic changes; (2) lack of inflammation, only occasional macrophages present and (3) absence of vascularisation. None of the patients had a history of active CMV infection. CONCLUSION: CMV infection is not limited as endotheliitis, but extends into the corneal stroma, and is a potential reservoir for graft infection, especially in partial thickness endothelial surgery. Clinical features are often non-specific, although glaucoma was present in our patients. CMV-infected grafts showed CD163-positive M2 macrophages in close association with the infected keratocytes, suggesting that the macrophage may be important in CMV graft infection. Histological examination with CMV IHC is a useful method to detect CMV infection postoperatively. Post penetrating keratoplasty, CMV systemic treatment with valganciclovir can prevent graft infection and failure. Boston keratoprosthesis may be a potential alternative surgery in active CMV infections that obviates the need for systemic therapy.

A common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome.

Exfoliation syndrome (XFS) is the most common recognizable cause of open-angle glaucoma worldwide. To better understand the etiology of XFS, we conducted a genome-wide association study (GWAS) of 1,484 cases and 1,188 controls from Japan and followed up the most significant findings in a further 6,901 cases and 20,727 controls from 17 countries across 6 continents. We discovered a genome-wide significant association between a new locus (CACNA1A rs4926244) and increased susceptibility to XFS (odds ratio (OR) = 1.16, P = 3.36 × 10(-11)). Although we also confirmed overwhelming association at the LOXL1 locus, the key SNP marker (LOXL1 rs4886776) demonstrated allelic reversal depending on the ancestry group (Japanese: OR(A allele) = 9.87, P = 2.13 × 10(-217); non-Japanese: OR(A allele) = 0.49, P = 2.35 × 10(-31)). Our findings represent the first genetic locus outside of LOXL1 surpassing genome-wide significance for XFS and provide insight into the biology and pathogenesis of the disease.

Expression of the primary angle closure glaucoma (PACG) susceptibility gene PLEKHA7 in endothelial and epithelial cell junctions in the eye.

PURPOSE: The role of the recently identified primary angle closure glaucoma (PACG) susceptibility gene, pleckstrin homology domain containing, family A member 7 (PLEKHA7), in PACG is unknown. PLEKHA7 associates with apical junctional complexes (AJCs) and is thus implicated in paracellular fluid regulation. We aimed to determine PLEKHA7's localization in the eye and its association with AJCs to elucidate its potential role in PACG. METHODS: Total RNA from ocular tissues was isolated and analyzed by real-time PCR. Frozen and paraffin-embedded human globes were sectioned and used for immunohistochemistry and immunofluorescence analysis. RESULTS: Specific PLEKHA7 expression was found in the muscles, vascular endothelium, and epithelium of the iris, ciliary body and ciliary processes, trabecular meshwork (TM), and choroid. PLEKHA7 expression in musculature and vascular endothelium was confirmed with smooth muscle marker, SMA, and endothelium marker, PECAM-1, respectively. At the above sites, PLEKHA7 colocalization was seen with adherens junction markers (E-cadherin and ß-catenin) and tight junction markers (ZO-1). CONCLUSIONS: Specific localization of PLEKHA7 was found within PACG-related structures (iris, ciliary body, and choroid) and blood-aqueous barrier (BAB) structures (posterior iris epithelium, nonpigmented ciliary epithelium, iris and ciliary body microvasculature). The association of PLEKHA7 with AJCs in the eye suggests a potential role for PLEKHA7 in PACG via fluidic regulation. Novel expression of PLEKHA7 was also seen in the ocular smooth muscles and vascular endothelia.

Confocal microscopy findings in deep anterior lamellar keratoplasty performed after Descemet's stripping automated endothelial keratoplasty.

BACKGROUND: This study describes the in vivo confocal microscopy findings in two patients who had deep anterior lamellar keratoplasty (DALK) following Descemet's stripping automated endothelial keratoplasty (DSAEK). METHODS: The study reviewed the cases of two patients who first underwent DSAEK followed by DALK when their vision failed to improve due to residual stromal scarring. In the first case, a DSAEK was performed for a patient with pseudophakic bullous keratopathy. After surgery, the patient's vision failed to improve satisfactorily due to residual anterior stromal opacity and irregularity. Subsequently, the patient underwent a DALK. The same two consecutive operations were performed for a second patient with keratoconus whose previous penetrating keratoplasty had failed and had secondary graft ectasia. In vivo confocal microscopy was performed 2 months after the DALK surgery in both cases. RESULTS: At 3 months after DALK, the best-corrected visual acuity was 6/30 in case 1 and 6/24 in case 2. In vivo confocal microscopy in both cases revealed the presence of quiescent keratocytes in the stroma layers of the DSAEK and DALK grafts, which was similar in the central and peripheral cornea. There was no activated keratocytes or haze noted in the interface between the grafts. CONCLUSION: Our short-term results show that performing a DALK after a DSAEK is an effective way of restoring cornea clarity in patients with residual anterior stromal opacity. In vivo confocal microscopy showed that there were no activated keratocytes seen in the interface of the grafts, which suggests that optimal visual acuity may be obtained with minimal interface haze.

Review for disease of the year: immunopathogenesis of ocular sarcoidosis.

Ocular sarcoidosis is a heterogeneous disease having varied presentations and severities with genetic susceptibility playing a role. Sarcoidosis is characterized by the presence of noncaseating (non-necrotizing) granulomas in the affected organs or tissue systems. What causes these granulomas is not known, but current knowledge of the immunology of this enigmatic disease centers on a CD4 T helper type 1 cell response. This review deals with immunologic sequences that lead to the formation of sarcoid granulomas and explores the immunopathogenesis of ocular inflammation seen in patients with sarcoidosis.

Anterior segment optical coherence tomography evaluation of the integrity of clear corneal incisions: a comparison between 2.2-mm and 2.65-mm main incisions.

PURPOSE: To compare wound characteristics and integrity of the 2.2-mm and 2.65-mm clear corneal incisions. DESIGN: Prospective, randomized clinical trial. METHODS: Patients undergoing phacoemulsification with lens implant were randomized to receive a 2.2-mm or 2.65-mm temporal clear corneal incision. The incisions were evaluated at 2, 24, and 96 hours for gape and wound architecture using anterior segment optical coherence tomography and for integrity using the Seidel test. Squareness of an incision was calculated (ratio of the incision length to the width). RESULTS: There were 30 patients in each group. Both incision sizes were watertight, although a mild internal main wound gape was detected on anterior segment optical coherence tomography in 35 eyes (58.3%) at 2 hours. The smaller wound was more square (0.81; standard deviation [SD], 0.11) than the larger wound (0.62; SD, 0.08; P < .001, t test). The mean squareness of eyes without wound gape at 2 hours (0.66; SD, 0.11) was lower than those with a wound gape (0.75; SD, 0.14; P = .008). A squareness factor of 0.72 or more had a positive predictive value for presence of wound gape at 2 hours of 79.3% and a negative predictive value of 61.3%. One side port incision with squareness of 1.39 had a mild leak at 2 and 24 hours, but no gape was seen on anterior segment optical coherence tomography. CONCLUSIONS: Both the 2.2-mm and 2.65-mm clear corneal incisions clinically were competent, but the side port incision may leak. A truly square wound has a greater likelihood of being associated with internal wound gape at 2 hours after surgery, especially if the squareness factor is 0.72 or more.