Machine Learning to Analyze Factors Associated With Ten-Year Graft Survival of Keratoplasty for Cornea Endothelial Disease.

Purpose: Machine learning analysis of factors associated with 10-year graft survival of Descemet stripping automated endothelial keratoplasty (DSAEK) and penetrating keratoplasty (PK) in Asian eyes. Methods: Prospective study of donor characteristics, clinical outcomes and complications from consecutive patients (n = 1,335) who underwent DSAEK (946 eyes) or PK (389 eyes) for Fuchs' endothelial dystrophy (FED) or bullous keratopathy (BK) were analyzed. Random survival forests (RSF) analysis using the highest variable importance (VIMP) factors were determined to develop the optimal Cox proportional hazards regression model. Main outcome measure was 10-year graft survival with RSF analysis of factors associated with graft failure. Results: Mean age was 68 ± 11 years, 47.6% male, in our predominantly Chinese (76.6%) Asian cohort, with more BK compared to FED (62.2 vs. 37.8%, P < 0.001). Overall 10-year survival for DSAEK was superior to PK (73.6 vs. 50.9%, log-rank P < 0.001). RSF based on VIMP (best Harrell C statistic: 0.701) with multivariable modeling revealed that BK (HR:2.84, 95%CI:1.89-4.26; P < 0.001), PK (HR: 1.64, 95%CI:1.19-2.27; P = 0.002), male recipients (HR:1.75, 95%CI:1.31-2.34; P < 0.001) and poor pre-operative visual acuity (HR: 1.60, 95%CI:1.15-2.22, P = 0.005) were associated with graft failure. Ten-year cumulative incidence of complications such as immune-mediated graft rejection (P < 0.001), epitheliopathy (P < 0.001), and wound dehiscence (P = 0.002) were greater in the PK compared to the DSAEK group. Conclusion: In our study, RSF combined with Cox regression was superior to traditional regression techniques alone in analyzing a large number of high-dimensional factors associated with 10-year corneal graft survival in Asian eyes with cornea endothelial disease.

Endothelial keratoplasty with anterior chamber intraocular lens versus secondary posterior chamber intraocular lens.

AIM: To describe the long-term outcomes of Descemet stripping automated endothelial keratoplasty (DSAEK) with an anterior chamber intraocular lens (ACIOL) compared to secondary posterior chamber (PC) IOL. METHODS: This was a retrospective comparative cohort study. The clinical data of 82 eyes from 82 consecutive patients with pseudophakic (PBK) or aphakic bullous keratopathy (ABK) who either underwent DSAEK with retained or secondary ACIOL (n=23) or DSAEK with IOL exchange and/or secondary PCIOL (retropupillary iris-claw IOL, n=25; intrascleral-fixated IOL, n=29; or sulcus IOL, n=5) were analysed. The main outcome measures were graft survival and complications up to 5 years. RESULTS: The graft survival in the secondary PCIOL group was superior than the ACIOL group over 5 years (year 1, 100.0% vs 100.0%; year 3, 94.7% vs 75.0%; year 5, 91.1% vs 60.6%, p=0.022). The presence of an ACIOL was a significant risk factor associated with graft failure (HR, 4.801; 95% CI, 1.406 to 16.396, p=0.012) compared to a secondary PCIOL. There was no significant difference in the rate of graft detachment and elevated intraocular pressure between the groups. There were five cases (9.3%) of IOL subluxation or dislocation in the retropupillary iris-claw and intrascleral-fixated IOL groups. CONCLUSIONS: Eyes that underwent DSAEK with ACIOL in situ had poorer long-term graft survival compared with those with secondary PCIOL. Intraocular lens exchange was not associated with a higher complication rate. In ABK or PBK eyes with ACIOL, we recommend performing IOL exchange and/or secondary PCIOL implantation combined with endothelial keratoplasty.

Clinical operational considerations and responses to lockdown and reopening in the Covid-19 pandemic: experience of a tertiary ophthalmology centre in Singapore.

BACKGROUND: Much has been written on infection control and clinical measures for ophthalmic institutions and departments to cope with the COVID-19 pandemic. However, few articles have detailed implementation plans to manage lockdowns and subsequent re-openings. In this article, specific operational responses and their outcomes in a large tertiary ophthalmology centre are described. METHOD: Through a concerted effort led by a dedicated task force, the Singapore National Eye Centre (SNEC) planned and executed an operational transformation to respond to the restrictions imposed on healthcare delivery during a national lock down. A carefully calibrated re-starting of services was carried out with the subsequent phased reopening of the country, taking into consideration unique constraints faced at that time. Strategies for operating in the new normal environment were also developed. RESULTS: Outpatient attendances were safely and expediently reduced by 70% (8749 vs. 29,311) and 82% (5164 vs. 29,342) in April and May 2020, respectively, compared to the corresponding months in 2019. A correspondingly large reduction in surgical load was also achieved through a similar triaging and prioritization system. Through optimizing the center's use of space and time, as well as expanding on new models of care, a return to pre-pandemic patient load was achieved 3 months into the phased reopening of the country, and subsequently exceeded in the following months. CONCLUSION: The lessons gleaned from SNEC's experience may be useful for institutions currently facing the same challenges, and for future responses to COVID-19 resurgences or other pandemics.

Assessment and Management of Dry Eye Disease and Meibomian Gland Dysfunction: Providing a Singapore Framework.

ABSTRACT: The purpose of this article is to provide a framework for general ophthalmologists in Singapore to manage dry eye. This framework considers the evidence in the literature as well as recommendations from expert panels such as the Tear Film & Ocular Surface Society Dry Eye Workshop II and the Asia Cornea Society Workgroup.This article covers the assessment of patient medical history and ask triage questions to identify local and systemic causes of dry eye disease (DED), excluding other possible causes, as well as the risk factors for DED and ocular surface inflammation. Evaluation of clinical signs to establish the diagnosis of DED and differentiation from other causes of irritable, red eyes are described. Tests for understanding the underlying disease processes and severity of DED are also presented.Management of dry eye should involve patient education and engagement. Information about the natural history and chronic nature of DED should be provided to improve long-term management of the disease and enhance compliance. Aggravating factors should be removed or lessened.We provide a guide to determine the most appropriate treatment (or combination of treatments) based on the severity and cause(s) of the disease, as well as the patient's needs and preferences. The aim of the management is to relieve ocular discomfort and prevent worsening of symptoms and signs, as well as to optimize visual function and minimize structural ocular damage. We also discuss the systematic follow-up and assessment of treatment response, as well as monitoring side effects of treatment, bearing in mind continuous support and reassurance to patients.

The Effects of Donor-Recipient Age and Sex Compatibility in the Outcomes of Deep Anterior Lamellar Keratoplasties.

PURPOSE: Corneal transplantations are the commonest allogenic transplant surgeries performed worldwide. Transplantable grade donor cornea is a finite resource. There is thus an impetus for eye banks to optimize the use of each harvested cornea, and clinicians to minimize the risks of graft rejection and failure. With better survival and lower rejection rates, anterior lamellar keratoplasty has gained popularity as an alternative technique to full-thickness penetrating keratoplasty, for the treatment of corneal stromal diseases. This study evaluated the effects of donor-recipient age- and sex-matching on the outcomes of eyes that had undergone deep anterior lamellar keratoplasty (DALK) surgeries. DESIGN: Observational cross-sectional study (national corneal graft registry data). SUBJECTS: All DALK surgeries performed in a tertiary ophthalmic hospital over an 11-year period. METHODS: To analyse the effects of donor-recipient sex-matching, transplantations were classified as "presumed H-Y incompatible" (male donor to female recipient) or "presumed H-Y compatible" (all other donor-recipient sex combinations). For age-matching, differences in donor and recipient ages were calculated. Cox proportional hazards regressions were used to evaluate the influence of donor-recipient sex-matching and age-matching on graft failure and rejection. MAIN OUTCOME MEASURES: Rates of graft failure and rejection within each group. RESULTS: 401 eyes were included. 271 (67.6%) transplants were presumed H-Y compatible. 29 (7.2%) grafts failed and 9 (2.2%) grafts rejected. There were trends of lower hazard ratios (HRs) in graft failure and rejection in the presumed H-Y compatible group [HRs: 0.59 (95% CI 0.20-1.77, p = 0.34) and 0.93 (95% CI 0.22-3.89, p = 0.926), respectively]. Median difference in age between recipients and donors was 15.0 years (IQR -2.8-34.3). The HRs of graft failure and rejection were not influenced by donor-recipient age [HRs per 1-year increase in age difference: 0.995 (95% CI 0.98-1.01, p = 0.483) and 1.01 (95% CI 0.99-1.03, p = 0.394), respectively]. CONCLUSION: In eyes that had undergone DALK surgeries, no significant influence of donor-recipient sex- or age-matching on graft rejection and failure was observed. Without strong evidence and the limitations of obtaining sample sizes required for an adequately powered study, the benefits of sex- and age-matching of donors and recipients during graft allocation for DALK surgeries is currently inconclusive.

Comparative Study of Long-term Graft Survival Between Penetrating Keratoplasty and Deep Anterior Lamellar Keratoplasty.

PURPOSE: Endothelial failure and immunological graft rejection remain long-term complications leading to late graft failure in penetrating keratoplasty (PK). Deep anterior lamellar keratoplasty (DALK) has emerged as a viable alternative that enables preservation of the host's endothelial cells to eliminate risks of endothelial rejection and failure. The aim of this study was to compare long-term graft survival between PK and DALK. DESIGN: Retrospective clinical cohort study. METHODS: All consecutive primary grafts of DALKs (n = 362) and PKs (n = 307) performed for optical indications in a tertiary eye center from the ongoing, prospective Singapore Corneal Transplant Study. Ten-year graft survival outcomes were compared. Cases in which endothelial pathologies were diagnosed were excluded, as DALK was not performed for such cases. Main outcome measurements were mean graft survival rate. RESULTS: The survival rate for PK was 94.4%, 80.4%, and 72.0% at 1, 5, and 10 years, respectively; and 95.8%, 93.9%, and 93.9% at 1, 5, and 10 years, respectively, for DALK (P = .001). Patients who underwent PK developed more complications of glaucoma (29.3% vs. 11.6%, respectively; P < .001), allograft rejection (16.6% vs. 1.7%, respectively; P < .001), epithelial problems (10.4% vs. 5.5%, respectively; P = .018), and nonimmunological failure (7.8% vs. 1.9%, respectively; P < .001), compared to DALK. Rates of graft failure attributable to rejection (36.7% vs. 5.9%, respectively; P = .015) and endothelial failure (36.7% vs. 5.9%, respectively; P = .015) were lower in DALK. CONCLUSIONS: The 10-year graft survival for primary DALK was superior to that for PK for corneal pathologies with functional endothelium. Primary DALK resulted in fewer post-operative complications and lower rates of graft rejection and failure. This study strengthens the case in favor of performing DALK over PK when possible.

Long-term outcomes of hemi-automated lamellar keratoplasty.

IMPORTANCE: To describe long-term outcomes of hemi-automated lamellar keratoplasty (HALK). BACKGROUND: HALK is a hybrid anterior lamellar keratoplasty technique for corneas with anterior to mid-stromal scars and topographical irregularities. DESIGN: Prospective interventional case series. PARTICIPANTS: Thirty-five eyes of 35 consecutive patients undergoing HALK at a single tertiary referral centre from 2007 to 2016. METHODS: Patients were followed up for a mean period of 61.4 ± 29.2 months. MAIN OUTCOME MEASURE: Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), spherical equivalent (SE) and cylinder, endothelial cell density (ECD), central corneal thickness (CCT), graft survival and complications were analysed. RESULTS: The most common indications for HALK were scars because of contact lens associated infectious keratitis (29%), unknown origin (26%) or corneal dystrophies (14%). Five patients had a previous keratoplasty (n = 4; deep anterior lamellar keratoplasty, n = 1). Two HALKs failed at 22 and 32 months follow-up. No graft rejections occurred. UCVA improved from 0.91 ± 0.31 to 0.58 ± 0.35 and BSCVA from 0.66 ± 0.30 to 0.21 ± 0.20 logMAR (P < 0.001) at the last follow-up. Astigmatism (P = 0.2), SE (P = 0.8) and ECD (P = 0.4) did not change significantly during follow-up. CCT increased from 490 to 560 µm (P = 0.004). Kaplan-Meier estimated survival for all HALK cases was 90.6 (95% confidence interval 82.6-98.5) months with a survival probability of 96% at 12 months and 92% at 3, 5 and 7 years of follow-up. CONCLUSIONS AND RELEVANCE: HALK provides excellent graft survival in primary cases and in patients with prior keratoplasty as well as significant improvement in visual acuity with low complication rates.

Development of Selective Lamellar Keratoplasty within an Asian Corneal Transplant Program: The Singapore Corneal Transplant Study (An American Ophthalmological Society Thesis).

PURPOSE: To evaluate outcomes of anterior lamellar keratoplasty (ALK) and endothelial keratoplasty (EK) within the Singapore Corneal Transplant Study (SCTS), with the hypothesis that both ALK and EK are able to provide equivalent or improved clinical outcomes, compared to penetrating keratoplasty (PK), and to determine changing trends globally with other international databases. METHODS: Clinical data on all transplants performed was derived from our SCTS database, a prospective national keratoplasty registry, and clinical outcomes (graft survival, endothelial cell loss, complications, visual acuity) were compared between PK, ALK, and EK. Global trends on indications and forms of keratoplasty performed in 2011/2012 were obtained from national keratoplasty or eye banking registries, corneal/ophthalmological societies, national eye banks, and national ophthalmic institutions. RESULTS: Global rates of EK surgery vary widely, from 52% (Sweden) to 0% (South Africa), with higher adoption by industrialized countries. ALK adoption rates similarly vary from 28.7% (China) to 1.0% (Philippines). SCTS data show high adoption rates in Singapore: EK 44% and ALK 28%. Our surgical modifications to big-bubble deep anterior lamellar keratoplasty (DALK) surgery resulted in visual outcomes matching PK, and a low conversion to PK of 2.1%, whereas our evolving approaches to donor insertion in Descemet's stripping automated endothelial keratoplasty (DSAEK) show significant reduction in 1-year postoperative endothelial cell loss rates from 60% (folding), to 22% to 30% (Sheets Glide), to 15% (EndoGlide inserter). CONCLUSION: Improvements in various forms of ALK and EK surgery can lead to better visual outcomes, longer graft survival, and reduced complications, as compared to PK. Global trends suggest adoption of these procedures at different rates.

Sequential therapeutic penetrating keratoplasty with cryopreserved and fresh corneal tissue for severe infectious keratitis: a case-control study.

PURPOSE: Sequential therapeutic penetrating keratoplasty (TPK) using a cryopreserved cornea followed soon after by a fresh optical grade cornea for severe infectious keratitis may improve the survival of the optical graft. The aim of this study was to compare the therapeutic efficacy, visual outcomes, and graft survival for sequential TPK against TPK using a fresh optical grade cornea alone. METHODS: This was a retrospective case-control study. Case records were reviewed for clinical and surgical outcomes. RESULTS: Thirty-two eyes of 32 patients were included. Ten eyes underwent sequential TPK (TPK cases), and there were 22 age- and sex-matched controls, which underwent TPK with optical grade tissue alone. The mean interval between the TPK with the frozen cornea and the subsequent optical keratoplasty in the TPK cases was 16.8 ± 12.9 days. Therapeutic success, defined as the eradication of the primary infection, was achieved in all the TPK cases but only in 13 controls (59.1%) (P = 0.06). Graft survival at 1 year was better in the TPK cases than the controls (72.9% vs 53.8%). An improvement in Snellen acuity by at least 2 lines was more likely in the TPK cases than the controls (80% vs 14%; P = 0.001). CONCLUSIONS: Sequential TPK is an effective surgical therapy for active severe infectious keratitis and also helps to conserve valuable optical grade corneal tissue.

Anterior lamellar keratoplasty over penetrating keratoplasty for optical, therapeutic, and tectonic indications: a case series.

PURPOSE: To report a consecutive case series of patients who underwent anterior lamellar keratoplasty (ALK) over a preexisting penetrating keratoplasty (PK). DESIGN: Retrospective, interventional case series. METHODS: Eight patients (8 eyes) were identified from the Singapore Corneal Transplant Study database, in a single institution (Singapore National Eye Center) from patients who underwent ALK performed over a PK. Main outcome measures were final visual acuity (VA), graft failure (ALK, PK or both), successful restoration of tectonic integrity in tectonic indications, and eradication of infection in therapeutic cases. RESULTS: The indications for surgery were therapeutic in 3 patients, optical in 3 patients, and tectonic in 2 patients. Postoperatively the best-corrected visual acuity (BCVA) improved in 5 eyes and remained unchanged in 3 eyes. Mean VA improved significantly after ALK; the mean preoperative BCVA was 1.52 +/- 0.25 and the mean postoperative BCVA was 0.87 +/- 0.26 (P = .032). Three of the 8 eyes post-lamellar keratoplasty (LK) managed to attain a BCVA equal to post-PK BCVA. Two patients had suture micro-perforations while 1 patient required a repeat ALK for recurrence of infection. CONCLUSION: ALK may be a considered as a viable alternative to a repeat PK for a variety of optical, therapeutic, and tectonic indications.

Paradigm shifts in corneal transplantation

Conventional corneal transplantation, in the form of penetrating keratoplasty (PK), involves full-thickness replacement of the cornea, and is a highly successful procedure. However, the cornea is anatomically a multi-layered structure. Pathology may only affect individual layers of the cornea, hence selective lamellar surgical replacement of only the diseased corneal layers whilst retaining unaffected layers represents a new paradigm shift in the field. Recent advancements in surgical techniques and instrumentation have resulted in several forms of manual, microkeratome and femto-second laser-assisted lamellar transplantation procedures. Anterior lamellar keratoplasty (ALK) aims at replacing only diseased or scarred corneal stroma, whilst retaining the unaffected corneal endothelial layer, thus obviating the risk of endothelial allograft rejection. Posterior lamellar keratoplasty/endothelial keratoplasty (PLK/EK) involves the replacement of the dysfunctional endothelial cell layer only. Whilst significant technical and surgical challenges are involved in performing lamellar micro-dissection of a tissue which is only 0.5 mm thick, the benefits of a more controlled surgical procedure and improved graft survival rates have resulted in a shift away from conventional PK. This review details the current advances in emerging lamellar corneal surgical procedures and highlights the main advantages and disadvantages of these new lamellar corneal procedures.

Iris reconstruction in penetrating keratoplasty--surgical techniques and a case-control study to evaluate effect on graft survival.

PURPOSE: To demonstrate techniques of iris reconstruction (pupilloplasty) at the time of penetrating keratoplasty (PKP) for a variety of pupil abnormalities, and to evaluate the effect of pupilloplasty on graft survival and visual outcome. DESIGN: Case-control study. METHODS: Thirty-five cases (combined PKP and pupilloplasty) and 70 controls (PKP alone) were included. Various pupil abnormalities and the surgical techniques used to correct them were reviewed and categorized. The Chi-square and Student t tests were used to compare the baseline risk factors and demographic variables between treatment and control groups. The known risk factors for corneal graft survival were analyzed by Kaplan-Meier and Cox regression methods. RESULTS: Twenty men and 15 women in the age range, 27 to 77 years underwent combined iris reconstruction and PKP with pseudophakic/aphakic bullous keratopathy being the most common indication. The mean follow-up duration was 39.12 months and eight (22.9%) grafts failed during follow-up. Iris reconstruction during PKP has a significant positive effect on long-term graft survival (hazard ratio 2.52; 95% CI, 1.14 to 5.57; P = .022). Patients with pupilloplasty also tended to have a better mean postoperative visual acuity compared to the control group (P = .40). CONCLUSIONS: Iris reconstruction is a relatively simple procedure that should be performed in eyes with substantial pupil abnormalities at the time of PKP. Pupilloplasty significantly improves graft survival, renders the pupil cosmetically more acceptable, and may improve visual outcome.