JOURNAL OF CORNEA

Diagnostic Criteria for Terrien Marginal Degeneration: Nordic Terrien Degeneration Study

Ruutila, Minna MD, FEBO*; Fagerholm, Per MD†; Lagali, Neil PhD†; Hjortdal, Jesper MD‡; Bram, Thue MD‡; Moilanen, Jukka MD, FEBO*; Kivelä, Tero T. MD, FEBO*

Abstract

Purpose: 

To refine the diagnostic criteria for Terrien marginal degeneration (TMD) based on experience in 3 Nordic countries.

Methods: 

This is a retrospective, multicenter, hospital-based cross-sectional study of 49 eyes of 29 white patients in tertiary referral centers in Finland, Sweden, and Denmark from 1998 to January 2018. The median follow-up was 3 years. Symptoms, best corrected visual acuity, astigmatism, corneal thickness, curvature and cavities, stage, and progression were analyzed.

Results: 

TMD was diagnosed equally likely between 15 and 86 years of age (median, 47 years). Twenty patients (69%) had bilateral disease, and 62% were men. Seventeen patients (59%) had symptoms including blurred vision and ocular surface disease symptoms without inflammatory signs. Eight patients (28%) had slightly reduced corneal sensitivity. Median best corrected visual acuity was 20/25 (range, 20/16–۲۰/۲۰۰) and astigmatism was 2.6 diopters (D) (range, 0–۱۰) with a mean progression of 0.41 D per year (range, 0–۵.۴). Age and astigmatism were not correlated. All eyes had peripheral vascularization, lipid deposits, and hyperreflectivity throughout thinned peripheral stroma and its anterior edge. The thinning progressed in 15 patients (52%). Of 26 patients, 8 (31%) had single or confluent paralimbal intrastromal cavities, most commonly superiorly. By Süveges classification, the stage was 2 (92%) or 3 (8%). Minimum corneal thickness and corneal curvature were loosely associated, leading to different stages in Wang classification in 34 eyes (69%).

Conclusions: 

TMD is defined by peripheral corneal thinning, superficial neovascularization, lipid deposition at the leading edge, absence of ulceration and inflammation, and frequently cavitation. The most sensitive way to follow its progression is anterior segment optical coherence tomography.

Interferon Alfa-2b for Pigmented Ocular Surface Squamous Neoplasia: A Report of 8 Lesions

Kaliki, Swathi MD; Sharma, Abhimanyu MD; Vempuluru, Vijitha S. MD

Abstract

Purpose: 

To study the efficacy of interferon alfa-2b (IFN-a2b) on pigmented ocular surface squamous neoplasia (p-OSSN) and assess the resolution of the pigment to the treatment.

Methods: 

A retrospective case series of 8 tumors in 7 patients.

Results: 

The mean age at diagnosis of p-OSSN was 65 years (median, 61 years; range, 51–۸۴ years), and all patients were men. The mean duration of symptoms was 2 months (median, 1 month; range, 1–۴ months). One patient had 2 distinct lesions in the same eye. Tumor epicenter was located at the limbus (n = 5) or bulbar conjunctiva (n = 2). Complexion-associated melanosis was noted in all eyes. The mean basal dimension of the tumor was 8 mm (median, 7 mm; range, 5–۱۲ mm). The mean % of tumor pigmentation was 47% (median, 30%; range, 10%–۱۰۰%). The treatment details included topical IFN-a2b (n = 1) or a combination of topical and subconjunctival injection of IFN-a2b (n = 7). All patients with p-OSSN showed excellent response to IFN-a2b with complete tumor regression and resolution of tumor-associated pigment with a mean number of 2 subconjunctival IFN-a2b injections (median, 2; range, 0–۳) and topical IFN-a2b for an average of 2 months (median, 2 months; range, 1–۳ months). There was no change in the complexion-associated melanosis with IFN-a2b.

Conclusions: 

IFN-a2b is very effective in the management of p-OSSN. There is a complete resolution of the pigment along with the tumor.

Corneal Crosslinking to Regress Pathologic Corneal Neovascularization Before High-Risk Keratoplasty

Schaub, Friederike MD*; Hou, Yanhong MD, PhD*,†,‡; Zhang, Wei MD*; Bock, Felix PhD*; Hos, Deniz MD, PhD*,§; Cursiefen, Claus MD, PhD*,§

Abstract

Purpose: 

Corneal neovascularization is the main risk factor for graft rejection after high-risk penetrating keratoplasty (PK). Corneal crosslinking (CXL) has been shown to regress pathological corneal blood and lymphatic vessels and to reduce the risk of graft rejection after high-risk PK experimentally in mice. The aim of this work was to analyze whether CXL is also able to regress corneal neovascularization in patients and is a safe procedure in the context of high-risk PK.

Methods: 

This retrospective case series included 5 patients with progressive corneal neovascularization and the need for high-risk PK because of graft rejection and/or keratitis that received CXL and PK between April 2019 and January 2020. CXL was performed before or in combination with PK and the effect of CXL on corneal neovascularization was assessed morphometrically on slit-lamp images. Patients were followed up to determine the incidence of adverse effects and graft rejection.

Results: 

In 1 case, peripheral corneal CXL was performed first as a single procedure, followed by an additional peripheral CXL procedure combined with PK. In all other cases, peripheral CXL was directly combined with PK. No intraoperative or postoperative complications were observed. Peripheral CXL resulted in a reduction of corneal neovascularization (mean reduction of 70.5% ± ۲۲.۷%). Revascularization was not observed. All transplants remained clear and without immune reactions (mean follow-up 16.4 ± ۱۴.۹ weeks, range 4–۴۲ weeks).

Conclusions: 

CXL is able to reduce pathological corneal neovascularization and might therefore be a novel treatment option to improve graft survival after high-risk PK.

Long-term Outcomes of Punctal Cauterization in the Management of Ocular Surface Diseases

Wang, Yvonne MD; Carreno-Galeano, Jimena Tatiana MD; Singh, Rohan Bir MD; Dana, Reza MD, MPH, MSc; Yin, Jia MD, PhD, MPH

Abstract

Purpose: 

To evaluate the long-term outcomes of surgical occlusion of lacrimal puncta using thermal cautery in the management of ocular surface diseases.

Methods: 

We reviewed medical records of 80 consecutive patients from a single academic center who underwent punctal cauterization. Patient demographics, ocular history, symptoms, and signs of ocular surface diseases pre- and post-cauterization were recorded.

Results: 

A total of 80 patients (171 puncta) were included, with an average age of 59 years and a follow-up duration of 27 months. The most common ocular morbidity was ocular graft-versus-host disease (n = 36), followed by primary keratoconjunctivitis sicca (n = 15). Indications for punctal cauterization included plug loss (n = 51), difficulty in plug fitting (n = 11), plug-related complications (n = 6), recanalization of previous cauterization (n = 7), and severe ocular surface disease requiring permanent punctal closure (n = 4). After punctal cauterization, the percentage of eyes with severe (21%) and moderate (25%) dry eye decreased significantly (8% and 19% at 3 months and 6% and 17% at 12 months, P = ۰.۰۰۰۶). Fifty-four percent of patients reported improvement in their symptoms. The rate of recanalization was 21% during the follow-up period. The use of topical corticosteroids was associated with higher recanalization rate. Associated complications were limited to temporary pain and swelling.

Conclusions: 

Punctal cauterization is an effective modality in treating severe ocular surface diseases in patients who repeatedly lose punctal plugs, and it can be easily performed in a clinic setting without major complications. However, cauterization may need to be repeated in up to a quarter of cases because of recanalization.

Comparative Analysis of Safety and Efficacy of Topography-Guided Customized Cross-linking and Standard Cross-linking in the Treatment of Progressive Keratoconus

Sachdev, Gitansha Shreyas MS, FICO, MRCSEd; Ramamurthy, Shreyas MS, FICO; B, Soundariya MS, FICO; Dandapani, Ramamurthy MD, FNAMS

Abstract

Purpose: 

To compare the safety and efficacy of topography-guided customized corneal cross-linking (PiXL) with standard cross-linking (CXL) for the treatment of progressive keratoconus.

Methods: 

In a prospective interventional analysis, the eyes of patients with progressive keratoconus underwent standard cross-linking (homogenous 9-mm ultraviolet-A irradiation of 9 mW/cm2 delivering a total fluence of 5.4J/cm2) versus topography-guided customized cross-linking (30 mW/cm2 pulsed irradiance with a total fluence ranging from 5.4 to 15 J/cm2, in concentric circles centered on the posterior float maximum). The following parameters were analyzed at the preoperative, 1-month, 6-month, and 1-year postoperative visits: corrected spectacle distance visual acuity, manifest refraction including sphere, cylinder and mean refractive spherical equivalent, corneal tomography, higher order aberration profile, and endothelial cell count. Anterior segment optical coherence tomography evaluation was performed at the 1-month postoperative visit to assess the depth of the demarcation line.

Results: 

Sixty-four eyes of 45 patients (32 eyes in each group) were included. There was a significant reduction in maximum keratometry and IS asymmetry in the PiXL group at both the 6-month and 1-year postoperative visits (P = ۰.۰۰۱ and 0.06). Corrected spectacle distance visual acuity improved significantly in the PiXL (0.05 ± ۰.۰۸ logarithm of the minimum angle of resolution, P = ۰.۰۲) versus the standard CXL (0.01 ± ۰.۰۲۵ logarithm of the minimum angle of resolution, P = ۰.۲۶) group. A greater depth of a stromal demarcation line was observed in the customized CXL group (P = ۰.۰۲). No significant complications were noted in either cohort.

Conclusions: 

PiXL demonstrated similar safety with significantly greater keratometry flattening and corneal regularization vis-à-vis standard CXL. This resulted in significant improvement of spectacle corrected visual acuity for eyes with mild-to-moderate keratoconus.

Y-27632 Promotes the Repair Effect of Umbilical Cord Blood-Derived Endothelial Progenitor Cells on Corneal Endothelial Wound Healing

Zhang, Weijie MD, PhD; Shao, Chunyi MD, PhD; Yu, Fei MD, PhD; Chen, Junzhao MD, PhD; Fu, Yao MD, PhD; Fan, Xianqun MD, PhD

Abstract

Purpose: 

To investigate the proliferation of umbilical cord blood–derived endothelial progenitor cells (UCB EPCs) and the differentiation efficiency toward corneal endothelial cell (CEC)-like cells induced by rho-associated protein kinase (ROCK) inhibitor Y-27632 and to determine the most effective strategy for repairing corneal endothelium injuries in rabbits.

Methods: 

UCB EPCs were cultured in Endothelial Cell Growth Medium-2 (EGM-2) media or conditioned media (CM) from human CECs, with and without the addition of Y-27632. Bromo-deoxyuridine (BrdU) immunocytochemistry and cell counting kit-8 assays were used to examine the proliferation of the cells. Real-time polymerase chain reaction, western blot, and immunocytochemistry were used to detect the CEC markers. Nd:YAG laser was used to establish an appropriate endothelium injury model based on rabbit corneas. The following intracameral injections were then performed to repair the model: 100 μL Opti-MEM I reduced serum medium (model group), 2 × ۱۰۵ UCB EPCs diluted in 100 μL Opti-MEM I reduced serum medium (EPC group), 100 μM Y-27632 diluted in 100 μL Opti-MEM I reduced serum medium (Y-27632 group), and 2 × ۱۰۵ UCB EPCs supplemented with 100 μM Y-27632 (final volume 100 μL, EPC/Y-27632 group). The follow-up tests focused on corneal transparency, central corneal thickness, intraocular pressure, and in vivo confocal microscopy, which were performed to evaluate the healing of the wounds.

Results: 

Culturing UCB EPCs in CM supplemented with 10 μM Y-27632 resulted in higher proliferation rates compared with EGM-2 media and CM. There were significantly improved protein levels of Zona Occludens 1, N-cadherin, Na+-K+-ATPase α۱, Na+-K+-ATPase β۱, and Pax6 and improved mRNA levels of collagen type IV and VIII and AQP1. The combined intracameral injection of Y-27632 and UCB EPCs accelerated the recovery of corneal transparency, regression of corneal edema, and healing of the corneal endothelium compared with the injections of Y-27632 and UCB EPCs on their own.

Conclusions: 

Y-27632 not only promotes the proliferation of UCB EPCs but also contributes to differentiation of UCB EPCs toward CECs in the presence of CM. The intracameral injection of Y-27632 itself promotes the healing of corneal endothelium wounds. On this basis, supplementing UCB EPCs with Y-27632 accelerates the healing of corneal endothelium wounds.

Bilateral Corneal Perforation in a Patient Under Anti-PD1 Therapy

Ramaekers, Anaïs MD; Aspeslagh, Sandrine MD, PhD; De Brucker, Nele MD; Van Mierlo, Camille MD; ten Tusscher, Marcel MD, PhD; Schauwvlieghe, Pieter-Paul MD; Termote, Karolien MD

Abstract

Immune checkpoint inhibition has improved the clinical outcomes for numerous patients with cancer. However, the downside is a whole new spectrum of immune-related adverse events. We report a 68-year-old man with a history of nonsmall cell lung cancer presenting with a spontaneous corneal perforation in the right eye after 22 cycles of pembrolizumab. In addition, a chronic central nonhealing epithelial defect developed after performing a penetrating keratoplasty. Treatment with autologous serum drops resulted in complete healing of the corneal ulcer, where other conventional therapies had no effect. One month after reinitiating pembrolizumab therapy, our patient presented again with a corneal perforation in the fellow eye. This case describes relapsing sterile ulcerations associated with pembrolizumab use and presents an unexpected cure.

Systematic Review: Effects of Pterygium and Pingueculum on the Ocular Surface and Efficacy of Surgical Excision

Linaburg, Taylor BSc; Choi, Daniel MD; Bunya, Vatinee Y. MD, MSCE; Massaro-Giordano, Mina MD; Briceño, César A. MD

Abstract

Purpose: 

This systematic review examines the specific effects of pingueculum and pterygium on the ocular surface and evaluates the efficacy of surgical excision in reversing those effects.

Methods: 

A systematic review was performed according to the Preferred Reporting Items for the Systematic Review and Meta-Analyses statement and included 59 articles studying the effects of pterygium and pingueculum on the ocular surface as measured by tear break-up time (TBUT), Schirmer testing, tear osmolarity, Ocular Surface Disease Index (OSDI), and the effects of surgical removal on these ocular surface parameters.

Results: 

In most studies, eyes with pterygium or pingueculum when compared with control eyes had a statistically significantly lower TBUT (average 3.72 s), lower Schirmer I without anesthesia (average 3.01 mm), lower Schirmer II (average 4.10 mm), higher tear osmolarity (average 12.33 mOsm/L), and higher OSDI (average 6.82 points). Moreover, excision of pterygium and pingueculum led to a statistically significantly higher TBUT (average 3.15 s higher at 1 mo postexcision), lower tear osmolarity (average 3.10 mOsm/L lower at 3 mo postexcision), and lower OSDI score (average 2.86 points lower 1 mo postexcision) in most of the studies. The effect of excision on Schirmer test scores was equivocal because most studies did not reach significance.

Conclusions: 

Our data confirm the relationship between pterygium and pingueculum and abnormal tear function and symptoms of dry eye disease. Furthermore, the data suggest that tear film parameters might improve after surgical removal of pterygium or pingueculum. Future studies would be helpful in exploring the potential role of pterygium and pingueculum excision in the management of dry eye disease.