Update on Dry Eye Disease Treatment: Evidence From Randomized Controlled Trials.

ABSTRACT: Although the ultimate goal of dry eye disease (DED) management is to restore the ocular surface and tear film homeostasis and address any accompanying symptoms, addressing this is not an easy task. Despite the wide range of current treatment modalities targeting multiple aspects of DED, the available DED management literature is quite heterogeneous, rendering evaluation or comparison of treatment outcomes hard or almost impossible. There is still a shortage of well-designed, large-scale, nonsponsored, randomized, controlled trials (RCTs) evaluating long-term safety and efficacy of many targeted therapies individually or used in combination, in the treatment of identified subgroups of patients with DED. This review focuses on the treatment modalities in DED management and aims to reveal the current evidence available as deduced from the outcomes of RCTs.

TFOS Lifestyle: Impact of contact lenses on the ocular surface.

Several lifestyle choices made by contact lens wearers can have adverse consequences on ocular health. These include being non-adherent to contact lens care, sleeping in lenses, ill-advised purchasing options, not seeing an eyecare professional for regular aftercare visits, wearing lenses when feeling unwell, wearing lenses too soon after various forms of ophthalmic surgery, and wearing lenses when engaged in risky behaviors (e.g., when using tobacco, alcohol or recreational drugs). Those with a pre-existing compromised ocular surface may find that contact lens wear exacerbates ocular disease morbidity. Conversely, contact lenses may have various therapeutic benefits. The coronavirus disease-2019 (COVID-19) pandemic impinged upon the lifestyle of contact lens wearers, introducing challenges such as mask-associated dry eye, contact lens discomfort with increased use of digital devices, inadvertent exposure to hand sanitizers, and reduced use of lenses. Wearing contact lenses in challenging environments, such as in the presence of dust and noxious chemicals, or where there is the possibility of ocular trauma (e.g., sport or working with tools) can be problematic, although in some instances lenses can be protective. Contact lenses can be worn for sport, theatre, at high altitude, driving at night, in the military and in space, and special considerations are required when prescribing in such situations to ensure successful outcomes. A systematic review and meta-analysis, incorporated within the review, identified that the influence of lifestyle factors on soft contact lens dropout remains poorly understood, and is an area in need of further research. Overall, this report investigated lifestyle-related choices made by clinicians and contact lens wearers and discovered that when appropriate lifestyle choices are made, contact lens wear can enhance the quality of life of wearers.

Morphological and functional assessment of the tear film and meibomian glands in keratoconus.

PURPOSE: To evaluate morphological and functional state of the meibomian glands (MG) in keratoconus patients. METHODS: One hundred eyes of 100 keratoconus patients and 100 eyes of 100 age-matched control subjects were included into this study. Ocular Surface Disease Index (OSDI) scores, non-invasive break up time (NIBUT), findings of meibography, staining with fluorescein of the ocular surface, tear film break-up time (TBUT), and Schirmer I test were documented in all patients' eyes and control eyes and were compared between the groups . RESULTS: The mean TBUT and NIBUT were significantly lower, corneal staining and OSDI scores were statistically greater in the keratoconus group (p < 0.05). The mean meiboscore, partial gland, gland dropout and gland thickening scores for upper/lower eyelids were significantly greater in keratoconus patients than controls (p < 0.05). The NIBUT measurements significantly correlated with MG loss in upper/lower eyelids (p < 0.05). The severity of keratoconus seemed to correlate with meiboscore, partial gland, gland thickening scores in upper/lower eyelids. CONCLUSION: Our data suggests that corneal ectasia in keratoconus is related with alterations in ocular surface, tear film function and MG morphology. Early screening and treatment of MG dysfunction may improve ocular surface quality and allow better disease management in keratoconus patients.

Long-term visual, refractive, tomographic and aberrometric outcomes of corneal collagen crosslinking (CXL) with or without hypoosmolar riboflavin solution in the treatment of progressive keratoconus patients with thin corneas.

PURPOSE: To evaluate the long-term visual, refractive, tomographic, and aberrometric outcomes of corneal collagen crosslinking (CXL) with or without hypoosmolar riboflavin solution in the treatment of progressive keratoconus patients with thin corneas. METHODS: Charts of consecutive progressive keratoconus patients with thinnest corneal thickness less than 470 µm who underwent corneal collagen CXL with or without hypoosmolar riboflavin solution and using a standardized protocol for treatment and examinations were analyzed retrospectively. The indication for hypoosmolar riboflavin use was a central corneal thickness less than 400 µm as measured by ultrasound pachymetry after epithelial debridement and before exposure to ultraviolet A (UVA) light. Uncorrected distance visual acuity (UDVA), best spectacle-corrected distance visual acuity (CDVA), manifest refraction, slit lamp biomicroscopy, corneal tomography, corneal aberrometry, and endothelial cell counts were evaluated at baseline and yearly at all postoperative follow-up examinations until month 36. The outcomes of corneal CXL procedure performed using hypoosmolar riboflavin were compared to those performed using the standard procedure. RESULTS: Twenty-three eyes (19 patients) were treated using hypoosmolar riboflavin application, and 30 eyes (28 patients) were treated using the standard procedure. Compared to baseline, the mean UDVA, CDVA, and keratometric readings improved statistically significantly in both groups at postoperative year 3, without any statistically significant between-group differences. Progression was not observed in any patient eye in either group. No significant endothelial cell loss and no sight threating complication were observed in any patient eye. CONCLUSION: At 3 years follow-up, the safety and efficacy of CXL using hypoosmolar riboflavin solution seems to be similar to that of standard CXL in progressive keratoconic eyes with thin corneas. The visual, refractive, keratometric, tomographic and aberrometric outcomes of the two procedures were comparable, as well.

Clinical Performance of Samfilcon A Contact Lenses in Intensive Digital Device Users: A Multicenter, Prospective Clinical Study.

INTRODUCTION: To evaluate patient satisfaction with samfilcon A contact lenses (CLs) in intensive digital device users with myopia and to compare patient satisfaction with samfilcon A lenses to prior experience with senofilcon A or lotrafilcon B CLs. METHODS: This was a comparative, prospective, national study conducted at 14 centers in Turkey. Subjects were adults aged 18 and 45 years with myopia (range -0.25 D to -6.00 D) who spend a minimum of 3 hours viewing digital devices (e.g., computer, smartphone). A subgroup of patients were habitual lens wearers (senofilcon A or lotrafilcon B lens wear for at least 6 months prior to enrollment). The primary assessment was patient satisfaction with samfilcon A lenses (0-100 Likert scale). Secondary assessments included patient satisfaction with samfilcon A lenses compared to patients' habitual lenses, investigator satisfaction with samfilcon A lenses and investigator-evaluated slit lamp examination findings. RESULTS: Samfilcon A lenses were given high overall ratings from both patients and investigators, with a low incidence of ocular symptoms. Overall, patients were highly satisfied with samfilcon A lenses for comfort, vision and overall performance, and stated that they would consider wearing these lenses in the future. Among habitual senofilcon A or lotrafilcon B lens wearers, samfilcon A lenses were rated significantly better than the habitual lenses in regard to comfort, vision and overall performance. Investigator assessments were also highly favorable, both at initial fit and after 4 weeks of follow-up, with no significant findings noted on slit lamp examination. CONCLUSION: Samfilcon A lenses were rated highly by investigators in regard to fit, handling and slit lamp findings, and by novice and habitual lens wearers in regard to comfort, vision and overall performance. These results support the use of samfilcon A lenses among digital device users who seek day-long comfort and good visual acuity.

Pediatric versus Adult Corneal Collagen Crosslinking: Long-term Visual, Refractive, Tomographic and Aberrometric Outcomes.

PURPOSE: To comparatively evaluate the long-term visual, refractive, topographic and aberrometric outcomes of conventional corneal collagen crosslinking (CXL) in the management of pediatric versus adult progressive keratoconus patients. MATERIALS AND METHODS: Retrospective, cross-sectional review of consecutive progressive keratoconus cases of corneal standard CXL using a standardized protocol for treatment and examinations was performed. Best spectacle-corrected distance visual acuity (CDVA), manifest refraction, slit lamp biomicroscopy, corneal tomography, corneal aberrometry and endothelial cell counts were evaluated at baseline and yearly at all postoperative follow-up examinations after month-12. The outcomes were analyzed by dividing the patients into 2 age groups; pediatric (≤18 years) versus adult (>18 years). RESULTS: Eighty-eight eyes (54 patients) in the pediatric and 104 eyes (68 patients) in the adult age groups completed 3 years follow-up. Compared to baseline, the mean CDVA, manifest refraction, keratometric readings, tomographic and aberrometric parameters improved statistically significantly in both groups at postoperative year-3 and year-4, without any statistically significant between-group differences. No change in the mean endothelial cell density (p > .05), or no sight threating complication was encountered in any patient eye in either group. In a subset of patients who were followed for 4 years (71 eyes in the pediatric and 70 eyes in the adult age groups), the outcome analyses were again similar between-groups. CONCLUSION: Conventional corneal CXL effectively halts the progression of keratoconus in both pediatric and adult age groups in long-term follow-up with similar visual, refractive, tomographic and aberrometric efficacy in both groups.

Comparative 2-year outcomes of conventional and accelerated corneal collagen crosslinking in progressive keratoconus.

AIM: To compare the safety and efficacy of conventional versus accelerated (9 mW/cm2) corneal collagen crosslinking (CXL) in progressive keratoconus at the 2-year follow-up. METHODS: In this prospective study, consecutive progressive keratoconus patients were randomized to receive either conventional CXL (CCXL) or accelerated CXL (ACXL; using hydroxypropyl methylcellulose-assisted riboflavin imbibition for 10min at 9 mW/cm2). Visual, refractive, keratometric, topographic, and aberrometric outcomes and stromal demarcation line depth (DLD) measurements were compared at the end of a 2-year follow-up. RESULTS: Thirty-two eyes from 32 patients in the CCXL and 27 eyes from 27 patients in the ACXL groups completed 2-year follow-up. At 2y post-CXL, both uncorrected and corrected visual acuities improved significantly in both groups. The improvements in keratometric readings, flattening rate (flattening of the maximum keratometry more than 1 D), 3 topographic indices, and vertical coma were significantly better in the CCXL group compared to the ACXL group (P<0.05). The DLD as measured by anterior segment optical coherence tomography or in vivo confocal microscopy was better detectable and significantly deeper in the CCXL group compared to the ACXL group. The deeper DLD was found to be significantly correlated with improvements in the mean keratometry measurements. Progression was noted in 11.1% of eyes in the ACXL group, whereas progression was not observed in any patient eye in the CCXL group. CONCLUSION: In this prospective randomized study, ACXL is less effective in halting the progression of keratoconus at a 2-year follow-up compared to CCXL.

Correction of Irregular Astigmatism With New-Generation Hybrid Contact Lenses.

PURPOSE: To evaluate the safety, efficacy, and on-eye performance of new-generation hybrid contact lenses (HCLs) in visual rehabilitation of eyes with irregular astigmatism and rigid gas-permeable (RGP) contact lens intolerance or failure. METHODS: The charts of patients who had been fit with new-generation HCLs were retrospectively reviewed. The reason for HCL fit and previous method of correction were noted. After the initial on-eye evaluation, visual and refractive outcomes, slit-lamp biomicroscopy, and lens comfort were evaluated at the last follow-up examination. RESULTS: Forty-seven eyes of 33 patients could be fit successfully with EyeBrid silicone (LCS, Cane, France) or Airflex (SwissLens, Prilly, Switzerland) lenses. The mean number of trial lenses required for ideal fit was 1.4±0.6 (range; 1-3) lenses. The reason for fit was either centration problems with RGP lenses or RGP intolerance. Twenty-nine eyes of 20 patients (72.5%) continued wearing their lenses more than 10 hr a day and for more than 3 months. In these successful wearers, the visual acuity (VA) improved significantly compared with the baseline uncorrected and spectacle-corrected VA (P<0.01), and no serious adverse events were encountered during the mean follow-up period of 10.1±6.4 months. At the last follow-up examination, patients preferred the new-generation HCLs over their habitual correction in regard to both VA and quality (P<0.05). CONCLUSION: New-generation HCLs seem to provide a viable alternative for visual rehabilitation of irregular astigmatism in selected eyes with RGP intolerance or RGP failure. The ease of the fitting process similar to fitting soft toric lenses and high patient satisfaction seem to be major advantages of these designs.

Severe Dry Eye in CD25 Deficiency Syndrome.

CD25 deficiency (Interleukin-2 receptor alpha deficiency) is a rare subtype of combined B- and T-cell immunodeficiency. Recurrent infections and lymphocyte infiltration of multiple tissues are the main clinical presentations. Only four patients have been reported in whom ophthalmological findings were not described. In this article, ocular findings of CD25 deficiency in a 12-year-old child are highlighted.

TFOS DEWS II Tear Film Report.

The members of the Tear Film Subcommittee reviewed the role of the tear film in dry eye disease (DED). The Subcommittee reviewed biophysical and biochemical aspects of tears and how these change in DED. Clinically, DED is characterized by loss of tear volume, more rapid breakup of the tear film and increased evaporation of tears from the ocular surface. The tear film is composed of many substances including lipids, proteins, mucins and electrolytes. All of these contribute to the integrity of the tear film but exactly how they interact is still an area of active research. Tear film osmolarity increases in DED. Changes to other components such as proteins and mucins can be used as biomarkers for DED. The Subcommittee recommended areas for future research to advance our understanding of the tear film and how this changes with DED. The final report was written after review by all Subcommittee members and the entire TFOS DEWS II membership.

Morphology of the Corneal Limbus Following Standard and Accelerated Corneal Collagen Cross-Linking (9 mW/cm2) for Keratoconus.

PURPOSE: To evaluate the morphological features of the corneal limbus as measured by in vivo confocal microscopy (IVCM) following standard and accelerated corneal collagen cross-linking (CXL) for keratoconus. METHODS: Patients with progressive keratoconus scheduled to undergo standard CXL (group 1; 31 patients, 3 mW/cm, 370 nm, 30 minutes), or accelerated CXL (group 2; 20 patients, 9 mW/cm, 370 nm, 10 minutes) in the worse eye were included in this prospective study. Thirty eyes of 30 age-matched patients served as controls (group 3). All patient eyes underwent IVCM scanning of the central cornea and the inferior limbal area at baseline and 1, 3, and 6 months after CXL. RESULTS: After CXL, epithelial regrowth was complete by day 4 in both groups 1 and 2. There were no statistically significant differences between the baseline mean central corneal wing or basal cell density, limbus-palisade middle or basal cell densities of groups 1, 2, or 3. At postoperative months 1, 3, and 6, there were no statistically significant differences in either central or limbus-palisade epithelial cell densities or diameters in keratoconic eyes that underwent standard or accelerated CXL (P > 0.05). The morphology of the limbal cells was preserved as well. CONCLUSIONS: The morphology of limbus structures seems to be preserved following standard and accelerated CXL in short-term follow-up, as measured using IVCM.

Comparison of Efficacy of Two Different Topical 0.05% Cyclosporine A Formulations in the Treatment of Adenoviral Keratoconjunctivitis-Related Subepithelial Infiltrates.

Subepithelial infiltrates secondary to adenoviral keratoconjunctivitis may persist for years and cause blurred vision, halos, glare, and photophobia. These infiltrates arise from immune reaction against the virus, and few studies have reported topical cyclosporine A to be effective in the treatment of subepithelial infiltrates. Herein, we describe a patient with adenoviral keratoconjunctivitis-related subepithelial infiltrates who did not respond to treatment with a new topical cyclosporine A emulsion prepared with castor oil (Depores 0.05%; Deva Ilaç, Kocaeli, Turkey), while the FDA-approved nanoemulsion formulation provided improvement in symptoms and reduced the inflammatory reaction (Restasis 0.05%; Allergan, Irvine, Calif., USA).

Pediatric Corneal Collagen Cross-Linking: Long-Term Follow-Up of Visual, Refractive, and Topographic Outcomes.

PURPOSE: To evaluate the long-term visual, refractive, and topographic outcomes of corneal collagen cross-linking (CXL) in the management of pediatric keratoconus. METHODS: Forty eyes of 40 consecutive patients with progressive keratoconus aged below 19 years were enrolled in this prospective study. All patient eyes underwent CXL with the standard (Dresden) protocol. Uncorrected distance visual acuity, best spectacle-corrected distance visual acuity, manifest refraction, slit-lamp biomicroscopy, corneal topography, corneal aberrometry, and endothelial cell counts were evaluated at baseline and at all postoperative follow-up examinations until month 48. RESULTS: Mean age of patients was 15.2 ± 1.9 years (10-18 years). Follow-up was 4 years. The mean improvements in uncorrected distance visual acuity (from 0.9 ± 0.3 logMAR to 0.5 ± 0.3 logMAR) and best spectacle-corrected distance visual acuity (from 0.4 ± 0.2 logMAR to 0.1 ± 0.1 logMAR) were statistically significant at month 48 (P = 0.0001). The mean Kmax decreased from 58.4 ± 5.5 D at baseline to 57.0 ± 5.3 D at month 48 (P = 0.04). Significant improvements in topographic and elevation indices and corneal aberrations were also noted after postoperative month 6. There was no change in the mean endothelial cell density (P > 0.05), and there was no progression or sight-threatening complication in any patient eye. CONCLUSIONS: Corneal CXL seems to be safe and effective in halting the progression of keratoconus in pediatric patients at 4-year follow-up. In addition, the procedure provides improvements in visual, refractive, topographic, and corneal aberrometric measurements.

Outcome of Two Corneal Collagen Crosslinking Methods in Bullous Keratopathy due to Fuchs' Endothelial Dystrophy.

Four eyes of 2 patients with corneal edema due to Fuchs' endothelial dystrophy were treated with CXL using the standard protocol. Since no improvement in visual acuity, corneal clarity, thickness, or pain sensation was evident in any eye at month 12, 2 eyes of the 2 patients were retreated, this time, following intraoperative corneal dehydration with glycerol 70% drops. This retreatment also failed to produce any significant effect on vision, corneal clarity, thickness, or pain in either eye. Collagen crosslinking with the current protocols may not be effective in the management of eyes with corneal edema due to Fuchs' endothelial dystrophy. Further studies are required to establish the efficacy of CXL and optimize the technique and/or dehydration method utilized in these cases.

KeraSoft 3 contact lenses in corneal ectasia.

OBJECTIVE: To evaluate the safety, efficacy, and on-eye performance of KeraSoft 3 contact lenses (UltraVision) in ectatic corneal diseases. METHODS: The charts of patients who were fit with KeraSoft 3 were reviewed. The reason for KeraSoft 3 lens fit, the number of trial lenses required for ideal fit, centration, movement, and stabilization of the contact lens, uncorrected, spectacle-corrected, and contact lens-corrected visual acuities, slitlamp biomicroscopy findings, patient comfort, and daily duration of contact lens wear were evaluated. RESULTS: Seventy eyes of 40 patients were fit with the KeraSoft 3 lens. Indications included rigid gas permeable (RGP) lens intolerance in 41 eyes of 24 patients (58.5%), patients' desire to use soft contact lenses in 26 eyes of 14 patients (37.1%), and proud nebula in 3 eyes of 2 patients (4.4%). The number of trial lenses required for ideal fit was 1.2±0.4 lenses. Eleven patients (20 eyes, 29%) never purchased the contact lens, 15 patients (26 eyes, 37%) discontinued after purchasing, and 14 patients (24 eyes, 34%) continued successfully wearing their lenses. In the latter group, the visual acuity improved significantly (P<0.05) and no adverse events were encountered during the mean follow-up period of 10.0±9.8 months. At the last follow-up examination, patients rated comfort and visual acuity with their contact lenses as "very good" to "excellent," with a desire to continue wearing them. CONCLUSION: In refractive correction of corneal ectasia, KeraSoft 3 contact lenses seem to be a good alternative to RGP lenses before more sophisticated lenses such as hybrid or scleral lenses are tried.

Ultraviolet A and riboflavin therapy as an adjunct in corneal ulcer refractory to medical treatment.

OBJECTIVE: To present a case of corneal ulcer unresponsive to medical treatment, successfully treated with the use of ultraviolet (UV) A and riboflavin collagen crosslinking (CXL) administered twice. METHODS: A 68-year-old diabetic male patient was diagnosed with unilateral severe corneal ulcer. Gram and Giemsa stains and corneal culture results were performed twice, but no specific pathogen could be detected. The clinical presentation suggested fungal infection. The ulcer was unresponsive to extensive medical treatment administered for 10 days. There was an initial response to topical and intrastromal voriconazole administration; however, this was followed by reactivation. Therefore, UVA-riboflavin treatment was performed when the patient was still on medical therapy. RESULTS: The stromal infiltrate appeared inactive 1 week after UVA-riboflavin CXL treatment. However, reactivation was noticed on the second week, and a second UVA-riboflavin treatment was planned and performed 3 weeks after the first one. The epithelial defect disappeared, and the stromal infiltrate stayed inactive starting from the first week of the second UVA-riboflavin treatment until the last follow-up examination at month 6. CONCLUSION: The UVA-riboflavin CXL may be considered in the management of corneal ulcers unresponsive to medical management.

Comparison of corneal curvature and anterior chamber depth measurements using the manual keratometer, Lenstar LS 900 and the Pentacam.

PURPOSE: The purpose of this study was to compare keratometry and anterior chamber depth (ACD) measurements from the Lenstar LS 900 (Haag-Streit AG, Switzerland) and the Pentacam (Oculus, Weltzar, Germany), and compare the keratometry readings of these two systems to a manual keratometer (MK), (Haag-Streit, Switzerland). MATERIALS AND METHODS: In this prospective study, keratometry and ACD measurements were obtained in 50 eyes of 50 normal subjects with the Lenstar and the Pentacam. Keratometry was also measured using a MK. Correlation, comparison, and interdevice agreement was evaluated using intraclass correlation analysis, Wilcoxon test, and Bland-Altman plots. RESULTS: The keratometry and ACD measurements obtained from the Lenstar and the Pentacam showed excellent correlation. The mean interdevice differences in mean keratometry (Km) for the Lenstar and the Pentacam, the Lenstar and the MK, and the Pentacam and the MK were 0.39 D, 0.10 D, and 0.30 D respectively; and the 95% limits of agreement (LoA) for Km were 0.04-0.82 D; -1.90-2.10 D; and -2.30-1.70 D, respectively. The mean interdevice difference in ACD for the Lenstar versus the Pentacam was 0.09 mm, with 95% LoA of 0.23-0.05 mm. CONCLUSIONS: The ACD measurements obtained using the Lenstar and the Pentacam seem to be interchangeable, whereas, the keratometry measurements obtained using the Lenstar, Pentacam, and MK differ considerably, and are not interchangeable.

Evaluation of Scheimpflug imaging parameters in subclinical keratoconus, keratoconus, and normal eyes.

PURPOSE: To determine the efficacy of different Scheimpflug-imaging parameters in discriminating between subclinical keratoconus, keratoconus eyes, and normal eyes. SETTING: Department of Ophthalmology, Ankara University Faculty of Medicine, Ankara, Turkey. DESIGN: Comparative case series. METHODS: Pentacam Scheimpflug measurements were taken in eyes with mild to moderate keratoconus, subclinical keratoconus, or with myopic astigmatism (normal eyes). Several parameters provided by the software or derived from the elevation maps were evaluated and compared between the groups. The Mann-Whitney test, receiver-operating-characteristic (ROC) curves, and logistic regression analysis were used to compare the mean measurements and to evaluate the sensitivity and specificity of the parameters or constructed models. RESULTS: The corneal power and elevation measurements were statistically significantly higher and the cornea was significantly thinner in eyes with subclinical or clinical keratoconus than in normal eyes (P < .05). The ROC curve analysis showed high overall predictive accuracy of various elevation and thickness indices in discriminating ectatic corneas from normal corneas. Logistic regression analysis showed that the goodness of fit of a model using a combination of corneal power, thickness, and anterior elevation parameters was best in discriminating keratoconus eyes from normal eyes, whereas that of a model using a combination of corneal power, thickness, and posterior elevation was best in discriminating subclinical keratoconus eyes from normal eyes. CONCLUSION: Combined analysis of anterior and posterior corneal power, elevation, and thickness data provided by the Scheimpflug device effectively discriminated between ectatic corneas and normal corneas. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.