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.

Surgical Management of Corneal Hydrops: Case Series

Descemet's membrane (DM) rupture/detachments have traditionally been treated conservatively, with limited efficacy and a long rehabilitation period that significantly affects patients' vision and quality of life. Although there are no established gold standards for the timing and nature of treatment, with this series of 4 cases we aimed to highlight the importance of the current optimal intervention methods. The first two patients were treated with anterior chamber injection of isoexpansile 14% C3F8 due to acute hydrops associated with keratoglobus in the first case and keratoconus in the second case. The third patient had keratoglobus and chronic hydrops complicated by multiple stromal clefts detected on anterior segment optical coherence tomography, and the fourth patient had a chronic broad DM detachment which occurred after cataract surgery. Both of these patients were treated with intracameral C3F8 injection together with corneal compressive sutures. In all four cases, DM reattached completely and effectively with surgical intervention. Surgical management of DM rupture/detachment with intracameral gas injection and compressive corneal sutures seems to provide fast symptomatic relief and less healing-related corneal scarring with better visual rehabilitation, and may alleviate the need for corneal transplant surgery in this group of 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.

Risk factors for progression following corneal collagen crosslinking in keratoconus.

PURPOSE: To assess risk factors for progression following corneal collagen crosslinking (CXL) in eyes with keratoconus. METHODS: Charts of patients who developed progression following conventional CXL treatment (Dresden protocol) were retrospectively evaluated in two centers (Center 1 and Center 2). 871 eyes of a total of 676 patients were analyzed. Progression was defined as > 1 diopter (D) increase in maximum keratometry (Kmax) readings compared to baseline. RESULTS: Progression was noted in 20 eyes of 20 patients (progression rate 3%). The mean age of the patients was 17.65 ± 5.76 (11-34)-years-old, and the mean follow-up following CXL was 36.70 ± 25.72 (12-84)-months-old. The gender distribution was 13 (65%) females and seven (35%) males. Four eyes (20%) had mild, 13 eyes (65%) had moderate, and three eyes (15%) had severe keratoconus at baseline. Fifteen eyes (75%) had allergic conjunctivitis, and 20 eyes (100%) reported eye-rubbing. Cone location was central in 17 (85%) eyes, and peripheral in 3 (15%) eyes. A mean of 2.21 ± 1.30 D (1.00-5.30 D) steepening was determined at Kmax 6 to 82 months following CXL treatment. CONCLUSIONS: Progression rate was found to be higher in the patients under the age of 17 years, female gender, allergic conjunctivitis, high preoperative Kmax (> 57 D), thin corneas (< 430 µm). The majority of progressive patients were central cone and moderate keratoconus.

Cytarabine-Induced Corneal Toxicity: Clinical Features and Relief of Symptoms with Loteprednol Etabonate 0.5% in Two Patients

We report two patients who developed toxic keratopathy following high-dose cytarabine chemotherapy and whose symptoms resolved following topical loteprednol etabonate 0.5% treatment. A 25-year-old woman and a 26-year-old man with acute myeloid leukemia were referred to our department with symptoms of ocular discomfort, photophobia, and blurred vision after consolidation chemotherapy. Central corneal epithelial microcysts were observed bilaterally in both patients, and in vivo confocal microscopy showed highly reflective disseminated granular and irregular intraepithelial opacities, mainly in the basal epithelial layers. Loteprednol etabonate 0.5% relieved both patients' symptoms in less than a week, and the microcysts disappeared in 2 to 3 weeks of treatment. Although there is no standardized treatment protocol for cytarabine-induced corneal toxicity, dexamethasone 0.1% and prednisolone phosphate 1.0% were reported to be effective in the resolution of discomfort and symptoms. In the two patients we report herein, loteprednol etabonate 0.5% four times daily was also effective in suppressing the symptoms.

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.

ISOPT Clinical Hot Topic Panel Discussion on Cornea Anterior Segment Disease.

The cornea and its adnexa pose a unique situation of a tightly defined set of requirements for its function. This includes: transparency, perfect built to obtain appropriate refractive power, protective barrier from microbial invaders. Moreso, the cornea also endures extreme external physical conditions (temperature, high and low humidity, winds and alike). All these functions are maintained while preserving a constant state of homogenous wetting. Toward that end the cornea is equipped with an elaborated network of sensory neural network. While enabling the blinking reflex and maintaining the physiological steady state of wetting, this neural network also makes the cornea prone to the discomfort that with or without associated changes seen on medical examination. ISOPT Clinical 2018 discussion touched upon this hypercomplex situation, addressing the role of inflammation and its resulting discomfort in dry eye conditions. The discussion also engulfed the emerging neuropathic pain syndrome that is recently gaining more attention. Another related topic was the utilization of autologous serum tears and its ability to provide amelioration to desperate patients. Finally, the panel discussed the issue of treating corneal infection, including when and how to utilize steroids in the course of therapy. We assume the reader will find interest in this discussion that directly addresses issues seen day in and day out in our busy clinics.

The Role of Soft Contact Lens Wear on Meibomian Gland Morphology and Function.

PURPOSE: To evaluate the impact of soft contact lens (CL) wear on the morphology and function of the meibomian glands (MG). METHODS: One hundred seventy-three eyes of 87 soft CL wearers and 103 eyes of 55 age-matched healthy volunteers were included into this study. The patients were divided into 3 groups according to the total duration of lens wear: less than 3 years, 3 to 7 years, and more than 7 years. Ocular Surface Disease Index (OSDI) scores, slitlamp biomicroscopy findings, fluorescein staining of the ocular surface, tear film break-up time (BUT), Schirmer I test, and meibography findings were recorded in all patient eyes and were compared with controls. RESULTS: The mean meiboscores of the upper and lower eyelids were significantly higher in CL wearers compared with controls (P<0.05). The mean BUT and the mean MG expressibility were significantly lower, whereas the mean OSDI score, corneal staining scores, percentage of partial/complete gland loss, and percentage of thickened and curled MG in upper/lower lids were statistically significantly higher in CL wearers (P<0.05). Meiboscores were significantly higher in patients with a total lens wear duration of more than 3 years compared to those with less than 3 years of lens wear for both upper/lower lids (P<0.05). The earliest morphological change in the MG of CL wearers was MG thickening, and this parameter was the only meibography finding that had the highest diagnostic ability for MG dysfunction. CONCLUSION: Soft CL wear causes significant morphological and functional changes in MG with thickening of MG presenting an early diagnostic finding of MG dysfunction on meibography.

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.