Conjunctival T Cell Profile in Allogeneic Hematopoietic Stem Cell Transplant Patients after Instilling Topical Cyclosporine-A 0.1% Cationic Emulsion.

INTRODUCTION: To profile conjunctival T cell populations in allogeneic hematopoietic stem cell transplant (HSCT) patients after instillation of daily topical cyclosporine-A (CsA) 0.1% cationic emulsion (Ikervis), and to evaluate patients' tolerance to these eye drops. METHODS: Nineteen participants were prescribed Ikervis prophylaxis once daily to both eyes from 3-5 weeks pre-HSCT to 12 months post-HSCT. The outcome measure was conjunctival T cell proportions from flow cytometry after impression cytology. Covariates included visual acuity, intraocular pressure, slit lamp and fundal examination, dry eye (SPEED) and quality of life questionnaires, non-invasive keratograph tear break-up time (NIKBUT), conjunctival redness, meibography, lipid thickness, Schirmer test, tear cytokines, fluorescein staining, tear osmolarity, and meibomian gland expressibility. RESULTS: The conjunctival T cell analysis showed either stable or decreased proportions of conjunctival CD4 T cells at the last visit from baseline in compliant patients. CD4 proportions were increased in non-compliant patients and in the single patient who developed ocular graft-versus-host disease (GVHD). All patients were tolerant to Ikervis but 6/19 were not compliant. In the majority of patients, vision did not affect activities of daily living. Pre- and post-HSCT up to the last study visit, there was no statistically significant change in clinical covariates. Only one participant developed ocular GVHD at 9 months post-HSCT. CONCLUSION: Superficial conjunctival T cell profile reflects compliance to daily topical Ikervis eye drops and clinical ocular surface parameters in allogenic HSCT patients. Tolerance is comparable to other formulations of topical CsA in the first 12 months. GOV IDENTIFIER: NCT04636918. URL: https://clinicaltrials.gov/ct2/show/NCT04636918?cond=ocular+Graft+Versus+Host+Disease&cntry=SG&draw=2&rank=2 .

Relationship between dry eye symptoms and quality of life: associations and mediation analysis.

PURPOSE: (1) To determine the independent association of dry eye symptoms with health-related quality of life (HRQoL) in the Singapore population and (2) to further investigate which factors mediate this association. METHODS: In this cross-sectional study, 7707 participants were included. The presence of dry eye symptoms was defined as experiencing at least one out of the six symptoms either 'often' or 'all the time'. The EuroQoL-5 dimensions (EQ-5D) utility instrument (raw scores converted to UK time trade-off (TTO) values) was used to assess generic HRQoL and the overall score from the Visual Functioning Questionnaire for visual functioning. The association between dry eye symptoms and EQ-5D was investigated using multivariable linear regression, adjusting for demographic and socioeconomic information, comorbidities, systemic and ocular examinations results. Mediation analysis was used to determine whether certain factors mediated this association. RESULTS: After adjusting for relevant factors, those with dry eye symptoms had significantly lower HRQoL (difference in EQ-5D TTO: -0.062 (95% CI -0.073 to -0.050)), with the inability to open eyes affected the most (-0.101 (95% CI -0.161 to -0.042)), followed by a sandy sensation (-0.089 (95% CI -0.121 to -0.058)), a burning sensation (-0.070 (95% CI -0.105 to -0.036)), red eyes (-0.059 (95% CI -0.082 to -0.036)), a dry sensation (-0.058 (95% CI -0.072 to -0.044)) and crusting of eyelids (-0.040 (95% CI -0.071 to -0.008)). Visual functioning and the presence of recent falls accounted for 8.63% (4.98%-14.5%) and 2.93% (0.04%-5.68%) of the indirect relationship between dry eye and HRQoL, respectively. CONCLUSION: Dry eye symptoms were independently associated with poor HRQoL. Moreover, this was partly mediated by reduced visual functioning and experiencing recent falls. Our results suggest that efforts to reduce severity of dry eye symptoms are essential to optimise patients' overall functioning and well-being.

Therapeutic Contact Lenses in the Treatment of Corneal and Ocular Surface Diseases-A Review.

Therapeutic contact lenses (TCLs) are often used in the management of a wide variety of corneal and ocular surface diseases (OSDs). Indications of TCL include pain relief, enhancing corneal healing, corneal sealing, corneal protection, and drug delivery. For painful corneal diseases such as bullous keratopathy, epidermolysis bullosa, and epithelial abrasions/erosions, bandage contact lenses (BCLs) provide symptomatic relief. Postoperatively in photorefractive keratectomy or laser epithelial keratomileusis, BCLs also alleviate pain. In severe OSDs such as severe dry eye, Stevens-Johnson syndrome/toxic epidermal necrolysis, gas-permeable scleral contact lenses are often used to enhance corneal healing. BCLs are used post-keratoplasty, post-trabeculectomy, and post-amniotic membrane transplantation to enhance healing. BCLs, with or without glue adhesives, are used to seal small corneal perforations and sometimes also used as bridging treatment before penetrating keratoplasty in larger corneal perforations. In patients with eyelid conditions such as trichiasis, ptosis, and tarsal scarring, BCLs are also effective in forming a mechanical barrier to protect the cornea. A relatively new use for TCLs is in ocular drug delivery where TCLs are used to maintain therapeutic concentrations of medication on the ocular surface. Contraindications of the use of TCLs include infective keratitis, corneal anesthesia, and significant exposure keratopathy with inadequate eyelid position or movement. Complications of TCL include infective keratitis, corneal hypoxia and associated complications, corneal allergies and inflammation, and poor lens fit. Overall, TCLs are effective in the treatment of corneal and OSDs but contraindications and complications must be considered.

Three-Year Outcomes of Simultaneous Accelerated Corneal Crosslinking and Femto-LASIK for the Treatment of High Myopia in Asian Eyes.

PURPOSE: To determine the long-term visual outcomes of simultaneous femtosecond laser-assisted laser in situ keratomileusis (femto-LASIK) and accelerated cross-linking (CXL) [LASIK Xtra] for the treatment of high myopia. PATIENTS AND METHODS: All 163 consecutive eyes of 85 patients who underwent LASIK Xtra for the treatment of high myopia and/or myopic astigmatism (spherical equivalent ≥ -6.00 D) in Singapore National Eye Centre from the years 2013 to 2017 were included in this retrospective case series. Post-operative follow-up was up to 3 years. RESULTS: Of the 163 eyes, 67 were followed up for 1 year (mean 12.9 months), 69 for 2 years (mean 24.0 months) and 43 for 3 years (mean 36.4 months). Overall mean follow-up was 22.8 months (9-46 months). The mean pre-operative spherical equivalent (SE) was -8.60 ± 1.47 D [range: -11.75 to -4.75] (n = 163) and mean attempted correction SE was -8.84 ± 1.41 D [range: -11.88 to -5.25]. Most eyes (>95%) maintained an uncorrected distance visual acuity of 6/12 or better over 3 years. Visual outcomes were predictable with ≥95% of eyes achieving a SE correction within ± 1D of attempted correction over 3 years. There was a mild regression in SE refraction over 3 years with a mean of -0.10 ± 0.45 D three years post-operatively (p = 0.03). The safety index was >1.05 at 3 years follow-up. There were no significant post-operative complications though 24 eyes had mild haze and 2 eyes had grade 1 diffuse lamellar keratitis that resolved within 1 month. CONCLUSION: Our 3-year LASIK Xtra results show favorable safety, efficacy, predictability and stability outcomes in Asian patients with high myopia.

Current perspectives in the management of keratoconus with contact lenses.

Our aim is to review current and significant articles on contact lens wear in keratoconus patients. A comprehensive literature search of PubMed was performed for the following topics on contact lens wear in keratoconus patients: (1) characteristics of contact lens wearers, (2) safety and efficacy, (3) complications, (4) fitting techniques, (5) contact lens wear after procedures/surgeries, (6) patient satisfaction. A total of 104 studies were finally selected and reviewed. Gas permeable (GP) lens wear provided significantly better vision than glasses. Special cone design lenses had better patient comfort levels though there was no difference in best corrected visual acuity among the GP lenses. Soft lenses showed good efficacy for the treatment of mild-to-moderate keratoconus with newer designs improving visual performance such as customised hydrogel and novel pinhole lenses. Scleral and hybrid lenses provide good visual acuity and comfort for keratoconic patients previously intolerant to RGP lenses. RGP lens wear post-cross linking (CXL) is relatively well-tolerated. Contact lenses may still be required post intrastromal corneal ring procedures and post keratoplasty. Scheimpflug imaging and anterior segment optical coherent tomography (ASOCT) are useful in contact lens fitting. Computerized contact lens fitting techniques could reduce the chair time of lens fitting as well as improve comfort and visual performance. Contact lenses play an important role in the visual rehabilitation of keratoconus patients. New contact lens designs and materials have significantly expanded the available fitting options for keratoconus patients. Imaging technology can be utilized to guide contact lens fitting.

Review of Laser Vision Correction (LASIK, PRK and SMILE) with Simultaneous Accelerated Corneal Crosslinking - Long-term Results.

Purpose: Laser in-situ keratomileusis (LASIK), photorefractive keratectomy (PRK) and small-incision lenticule extraction (SMILE) are safe and effective refractive surgical procedures. However, complications include regression of treatment and iatrogenic keratectasia which can be severe and sight-threatening. In order to reduce these complications, simultaneous corneal cross-linking (CXL) is currently being added to these refractive procedures. This review analyses current long-term literature (≥ 1 year follow-up) on refractive surgery and simultaneous CXL (LASIK Xtra, PRK Xtra and SMILE Xtra) to determine its overall safety and efficacy.Methods: A comprehensive literature search of various electronic databases (PubMed, PubMed Central and MEDLINE) was performed up to 9th February 2019. Efficacy and safety indices are calculated where possible.Results: Ten relevant studies were found for LASIK Xtra, 4 for PRK Xtra and 1 for SMILE Xtra. The total number of eyes included in this review was 1,189: 347 eyes for LASIK Xtra, 300 eyes for LASIK-only, 298 for PRK Xtra, 204 for PRK-only, 40 for SMILE Xtra and none for SMILE-only. Current studies show that refractive surgery and simultaneous CXL produces comparable or better results in terms of refractive and keratometric stability than refractive surgery alone. However, case reports of complications such as corneal ectasia, diffuse lamellar keratitis and central toxic keratopathy have also recently been published.Conclusions: Simultaneous accelerated CXL and refractive surgery is effective for the treatment of myopia. However, it is as yet unclear if the additional CXL step reduces the incidence of iatrogenic keratectasia. Further long-term comparative studies would be useful in evaluating safety and efficacy of this procedure. More research should also be performed to titrate the UV-A irradiation settings for an optimal outcome.

Relationship Between Sleep and Symptoms of Tear Dysfunction in Singapore Malays and Indians.

Purpose: The purpose of this study was to investigate the association between sleep (duration and quality) and symptoms of dry eye in Singapore Malay and Indian adults. Methods: This was a prospective cross-sectional study. A total of 3303 subjects aged 40 years and above from two large population-based cohorts, the Singapore Malay Eye Study-2 (n = 1191, 2011-2013) and the Singapore Indian Eye Study-2 (n = 2112, 2013-2015), were included. The presence of symptoms of dry eye was defined as having at least one of six symptoms often or all the time. Sleep questionnaires included the Epworth Sleepiness Scale, Berlin Questionnaire, STOP-bang questionnaire, and Insomnia Severity Index. Poor sleep quality was defined as meeting the respective questionnaire thresholds. General health questionnaires (including sleep duration) and standardized ocular and systemic tests were also used. Results: Of 3303 participants, 6.4% had excessive sleepiness, 20.5% had high risk for sleep apnea, 2.7% had clinical insomnia, and 7.8% had <5 hours of sleep. These sleep factors were associated with symptoms of dry eye. After adjusting for relevant demographic, medical, and social factors, the following were associated with higher odds of symptoms of dry eye: excessive sleepiness (Epworth Sleepiness Scale: odds ratio [OR] = 1.77 [1.15-2.71]), high risk of sleep apnea (Berlin Questionnaire: OR = 1.55 [1.17-2.07], STOP-Bang Questionnaire: OR = 2.66 [1.53-4.61]), clinical insomnia (Insomnia Severity Index: OR = 3.68 [2.17-6.26]) and <5 hours of sleep (OR = 1.73 [1.17-2.57], reference sleep duration 5-9 hours). Sleep apnea, insomnia, and sleep duration were each shown to be independently associated with symptoms of dry eye. Conclusion: Short sleep duration and poor quality are both significantly and independently associated with symptoms of dry eye.

A Review of Corneal Collagen Cross-linking - Current Trends in Practice Applications.

OBJECTIVE: To review the literature on current applications of corneal Collagen Cross-Linking (CXL). METHODS: A review of publications on corneal cross-linking was conducted. This included systemic reviews, randomized controlled clinical trials, cohort studies, case-controlled studies and case series. A summary of the publications is tabulated. RESULTS: The original indication of riboflavin - Ultraviolet-A (UVA) induced corneal collagen cross-linking is to arrest the progression of keratoconus. Studies show that it is effective in arresting the progression of keratoconus and post-LASIK ectasia with the standard Dresden protocol (epithelium-off). There are also improvements in visual, keratometric and topographic measurements over time. Severe complications of cross-linking are rare. The epithelium-on techniques have less efficacy than the Dresden protocol. Accelerated protocols have variable results, with some studies reporting comparable outcomes to the Dresden protocol while other studies reporting less efficacious outcomes. Cross-linking combined with refractive procedures provide better visual outcome but long term studies are warranted. Cross-linking for the treatment of infective keratitis is a promising new treatment modality. Initial studies show that it is more effective for superficial rather than deep infections and for bacterial rather than fungal infections. CONCLUSIONS: Corneal cross-linking is a procedure with an expanding list of indications from the treatment of corneal ectasias to infective keratitis. While the standard Dresden protocol is established as the gold standard treatment for progressive keratoconus, the more recent protocols may require further refinements, investigative and long-term studies.