Francisco Amparo

Topical interleukin 1 receptor antagonist for treatment of dry eye disease: a randomized clinical trial.

IMPORTANCE The immunopathogenic mechanisms of dry eye disease (DED), one of the most common ophthalmic conditions, is incompletely understood. Data from this prospective, double-masked, randomized trial demonstrate that targeting interleukin 1 (IL-1) by topical application of an IL-1 antagonist is efficacious in significantly reducing DED-related patient symptoms and corneal epitheliopathy. OBJECTIVE To evaluate the safety and efficacy of treatment with the topical IL-1 receptor antagonist anakinra (Kineret; Amgen Inc) in patients having DED associated with meibomian gland dysfunction. DESIGN AND SETTING Prospective phase 1/2, randomized, double-masked, vehicle-controlled clinical trial. PARTICIPANTS Seventy-five patients with refractory DED. INTERVENTIONS Participants were randomized to receive treatment with topical anakinra, 2.5% (n = 30), anakinra, 5% (n = 15), or vehicle (1% carboxymethylcellulose) (n = 30) 3 times daily for 12 weeks. MAIN OUTCOMES AND MEASURES Primary outcomes were corneal fluorescein staining (CFS), complete bilateral CFS clearance, dry eye-related symptoms as measured by the Ocular Surface Disease Index, tear film breakup time, and meibomian gland secretion quality. RESULTS Topical anakinra was well tolerated compared with vehicle, with no reports of serious adverse reactions attributable to the therapy. After 12 weeks of therapy, participants treated with anakinra, 2.5%, achieved a 46% reduction in their mean CFS score (P = .12 compared with vehicle and P < .001 compared with baseline); participants treated with anakinra, 5%, achieved a 17% reduction in their mean CFS score (P = .88 compared with vehicle and P = .33 compared with baseline); and patients treated with vehicle achieved a 19% reduction in their mean CFS score (P = .11). Complete bilateral CFS clearance was noted in 8 of 28 patients (29%) treated with anakinra, 2.5%, vs in 2 of 29 patients (7%) treated with vehicle (P = .03). By week 12, treatment with anakinra, 2.5%, and treatment with anakinra, 5%, led to significant reductions in symptoms of 30% and 35%, respectively (P = .02 and P = .01, respectively, compared with vehicle); treatment with vehicle led to a 5% reduction in symptoms. CONCLUSIONS AND RELEVANCE Treatment with topical anakinra, 2.5%, for 12 weeks was safe and significantly reduced symptoms and corneal epitheliopathy in patients with DED. These data suggest that the use of an IL-1 antagonist may have a role as a novel therapeutic option for patients with DED. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00681109.

Optical analysis, reading performance, and quality-of-life evaluation after implantation of a diffractive multifocal intraocular lens.

PURPOSE: To evaluate the reading performance, changes in quality of life, and optical performance after cataract surgery with multifocal diffractive intraocular lens (IOL) implantation. SETTING: Vissum Corporation, Alicante, Spain. DESIGN: Prospective case series. METHODS: Patients with bilateral cataract had implantation of Acri.LISA 366D multifocal IOLs. Visual acuity and contrast sensitivity outcomes were evaluated during a 6‐month follow‐up. Other parameters evaluated included reading performance (Salzburg Reading Desk), a 25‐item quality‐of‐life questionnaire (National Eye Institute Visual Functioning Questionnaire‐25 [NEI VFQ‐25] and appendix NEI VFQ‐39), and ocular optical performance (ocular aberrometry and modulation transfer function). RESULTS: The study included 48 eyes (24 patients) ranging in age from 47 to 77 years. The mean uncorrected distance visual acuity (logMAR) improved significantly 1 month postoperatively (P<.01), with no significant changes afterward (6 months, P≥.06). The mean reading acuity without correction improved significantly from 0.68 logRAD ± 0.20 (SD) to 0.16 ± 0.08 logRAD 1 month after surgery (P < .01). However, it was worse by the end of the follow‐up (6 months, P = .04). During the follow‐up, no significant changes were found in the mean reading speed without near correction (6 months, P = .50). Contrast sensitivity improved significantly at all spatial frequencies under photopic and scotopic conditions after surgery (6 months, P≤.02). The quality‐of‐life index related to reading ability also improved significantly (3 months, P = .03). CONCLUSION: Implantation of the multifocal diffractive IOL significantly improved reading performance, which had a positive effect on the patient’s quality of life postoperatively. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned.

Pachymetric measurements with a new Scheimpflug photography-based system: intraobserver repeatability and agreement with optical coherence tomography pachymetry.

PURPOSE: To evaluate the intraobserver repeatability of pachymetric measurements obtained with a new Scheimpflug photography–based system and the agreement of the measurements with those obtained by optical coherence tomography (OCT). SETTING: Vissum Corporation, Alicante, Spain. DESIGN: Evaluation of diagnostic technology. METHODS: Corneal thickness was measured at different locations (center; 2.5 mm and 4.0 mm nasal, temporal, superior, and inferior) in 18 eyes of 18 patients with no ocular pathology or previous surgery with a Scheimpflug photography–based system (Sirius). Three consecutive measurements at each location were obtained with the system to evaluate intraobserver repeatability. Afterward, pachymetric measurements were obtained at the same locations with an OCT system (Visante) to evaluate the agreement between techniques using the Bland‐Altman method. RESULTS: The intraclass correlation coefficient of repeated measures ranged from 0.990 to 0.997. The coefficient of variation was lower than 1% and the standard deviations of the repeated measurements (Sw) were below 6 μm at all corneal locations. Statistically significant differences were found between the coefficient of variation and Sw values of the repeated measurements corresponding to the 2.5 mm and 4.0 mm locations (P≤.037). The agreement with OCT pachymetric measurements was poor, with ranges of agreement larger than 20 μm at all corneal locations. Statistically significant differences were found between standard deviations of the differences between the 2 devices at the 2.5 mm and 4.0 mm locations (P≤.017). CONCLUSION: Scheimpflug photography–based technology provided repeatable pachymetric measurements that were not equivalent to those obtained with OCT. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned.

Visual and Optical Performance With Two Different Diffractive Multifocal Intraocular Lenses Compared to a Monofocal Lens

PURPOSE To compare the visual acuity outcomes as well as the ocular optical performance of eyes implanted with either a monofocal or one of two diffractive multifocal intraocular lenses (IOLs). METHODS One hundred two consecutive eyes of 51 bilateral cataract patients (age 49 to 80 years) were divided into three groups: 22 eyes were implanted with a monofocal IOL (monofocal group), 40 eyes with the Acrysof ReSTOR SN6AD3 IOL (ReSTOR group), and 40 eyes with the Acri.Lisa 366D IOL (Acri.Lisa group). Visual acuity and contrast sensitivity were evaluated pre- and postoperatively. Additionally, ocular optical quality and intraocular aberrations were evaluated postoperatively. RESULTS Significant improvement after surgery in uncorrected and corrected distance and near visual acuity was observed in all three groups (P≤.05). Uncorrected near visual acuity was significantly better in eyes from the ReSTOR and Acri.Lisa groups compared to the monofocal group (P≤.01). Photopic contrast sensitivity was significantly better for the spatial frequency of 3 cycles/degree in the monofocal group (P<.01). Significantly higher values of the ocular Strehl ratio and cutoff modulation transfer function spatial frequency were also found in the Acri.Lisa group (P=.01). An acceptable range of vision between near and distance peaks was observed in the defocus curves of the ReSTOR and Acri.Lisa groups. CONCLUSIONS The AcrySof ReSTOR and Acri.Lisa 366D IOLs are able to successfully restore near and intermediate visual function after cataract surgery; however, the Acri.Lisa design seems to provide better optical performance. These results need to be confirmed in a randomized, prospective trial.

Quality of life evaluation after implantation of 2 multifocal intraocular lens models and a monofocal model

PURPOSE: To compare vision‐related quality of life using the National Eye Institute Visual Function Questionnaire (NEI VFQ‐25) in patients with 1 of 3 types of intraocular lenses (IOLs) and to correlate it with postoperative visual outcomes. SETTING: Vissum Corporation–Instituto Oftalmológico de Alicante, Alicante, Spain. DESIGN: Comparative case series. METHODS: This study comprised eyes having cataract surgery with bilateral implantation of a monofocal IOL (Group A), apodized multifocal IOL (Group B), or full diffractive multifocal IOL (Group C). Distance and near visual acuities, contrast sensitivity, and quality of life were evaluated preoperatively and postoperatively. RESULTS: The study enrolled 106 eyes (53 patients; age range 49 to 80 years). All groups had significant improvement in uncorrected and corrected distance visual acuities postoperatively (P≤.05). Near vision outcomes were significantly better in Groups B and C (P≤.01). Groups B and C had significantly less difficulty in some near tasks, such as reading the newspaper (A–B, P=.02; A–C, P=.02) or reading bills (A–B, P=.04; A–C, P=.004). Group C also had significantly less difficulty driving at night than Group B (P<.01). Near visual acuity and contrast sensitivity were significantly correlated with difficulty in near visual tasks in Groups B and C. Night‐driving difficulty correlated significantly with contrast sensitivity in Group B. CONCLUSIONS: Patients with multifocal IOLs could perform several daily tasks at near and intermediate distances, with less night‐driving limitation with the full diffractive IOL than with apodized multifocal and monofocal IOLs. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned.

Short-term topical bevacizumab in the treatment of stable corneal neovascularization.

PURPOSE To evaluate the safety and efficacy of topical bevacizumab in the treatment of corneal neovascularization. DESIGN Prospective, nonrandomized, interventional case series. METHODS setting: Institutional, multicenter clinical trial. study population: Twenty eyes from 20 patients with stable corneal neovascularization. intervention procedures: Patients were treated with topical 1.0% bevacizumab for 3 weeks and were monitored for a total of 24 weeks. main outcome measures: Primary outcome measures included: neovascular area, defined as the area of the corneal vessels themselves; vessel caliber, defined as the mean corneal vessel diameter; and invasion area, defined as the fraction of the total cornea into which the vessels extended. The occurrence of ocular and systemic adverse events was monitored closely. RESULTS As compared with the baseline visit, patients exhibited a statistically significant improvement in neovascular area by week 6 (P = .007) and in vessel caliber by week 12 (P = .006). At the final visit, neovascular area, vessel caliber, and invasion area were reduced by 47.5%, 36.2%, and 20%, respectively. The decreases in neovascular area and vessel caliber were statistically significant (P < .001 and P = .003, respectively); however, the reduction in invasion area did not reach statistical significance (P = .06). There were no significant changes in the secondary outcomes, and there were no adverse events. CONCLUSIONS Short-term topical bevacizumab treatment reduced the extent of stable corneal neovascularization as measured by neovascular area and vessel caliber with no associated adverse events. Interestingly, the degree of treatment efficacy was inversely proportional to the baseline invasion area.

Topical Ranibizumab as a Treatment of Corneal Neovascularization

Purpose: To examine the effect of topical ranibizumab on clinically stable corneal neovascularization (NV). Methods: This was a prospective, open-label, monocentric, uncontrolled noncomparative study. Ten eyes of 9 patients with corneal NV received topical ranibizumab (1%) 4 times a day for 3 weeks with a follow-up period of 16 weeks. The main corneal NV outcome measures were: neovascular area, the area occupied by the corneal neovessels; vessel caliber (VC), the mean diameter of the corneal neovessels; and invasion area (IA), the fraction of the total cornea area covered by the vessels. This study was conducted at the Massachusetts Eye and Ear Infirmary, Boston, MA. Results: Statistically significant decreases in neovascular area (55.3%, P < 0.001), which lasted through 16 weeks, and VC (59%, P < 0.001), which continued to improve up to week 16, were observed after treatment. No significant decrease was observed in IA (12.3%, P = 0.49). There was no statistically significant change in visual acuity or intraocular pressure. No adverse events ascribed to the treatment were noted. Conclusions: Topical application of ranibizumab is effective in reducing the severity of corneal NV in the context of established corneal NV, mostly through decrease in VC rather than IA.

Factors influencing corneal biomechanical changes after microincision cataract surgery and standard coaxial phacoemulsification

PURPOSE: To determine the factors affecting corneal biomechanics using biomechanical waveform analysis after microincision cataract surgery (MICS) and standard coaxial phacoemulsification with different incision sizes. SETTING: Vissum‐Instituto Oftalmologico de Alicante, Alicante, Spain. METHODS: This prospective nonrandomized study comprised eyes with significant cataract that had MICS (sub‐1.8 mm incision) or coaxial phacoemulsification (2.75 mm incision). Corneal hysteresis (CH) and the corneal resistance factor (CRF) were measured by biomechanical waveform analysis (Ocular Response Analyzer) preoperatively, immediately postoperatively, and at 1 month. Results were analyzed and compared between groups. RESULTS: In the MICS group (n = 30), there was a significant increase in Goldmann‐correlated intraocular pressure (IOP) and corneal‐compensated IOP, although CH decreased in the immediate postoperative period (P<.05). At 1 month, all parameters in the MICS group returned to normal. The coaxial group (n = 30) had an increase in Goldmann‐correlated IOP and corneal‐compensated IOP, both of which were higher than normal at 1 month. Backward multiple regression analysis showed significant correlations between CH and preoperative Goldmann‐correlated IOP and preoperative CRF (r2 = 0.631, P<.05); between age, axial length (AL), and preoperative CRF (r2 = 0.418, P<.05); and between the change in CH and AL, total incision length, and preoperative CH (r2 = 0.429, P<.05). CONCLUSIONS: Cataract surgery with MICS and coaxial phacoemulsification significantly altered corneal biomechanics. Corneal hysteresis was inversely correlated with Goldmann‐correlated IOP; CRF was inversely correlated with age and AL. The MICS technique provided more stable corneal biomechanical properties than standard coaxial phacoemulsification 1 month postoperatively. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned.

Cornea and Ocular Surface Treatment

In addition to being a protective shield, the cornea represents two thirds of the eyes refractive power. Corneal pathology can affect one or all of the corneal layers, producing corneal opacity. Although full corneal thickness keratoplasty has been the standard procedure, the ideal strategy would be to replace only the damaged layer. Current difficulties in corneal transplantation, mainly immune rejection and shortage of organ supply, place more emphasis on the development of artificial corneas. Bioengineered corneas range from prosthetic devices that solely address the replacement of the corneal function, to tissue-engineered hydrogels that allow regeneration of the tissue. Recently, major advances in the biology of corneal stem cells have been achieved. However, the therapeutic use of these stem cell types has the disadvantage of needing an intact stem cell compartment, which is usually damaged. In addition, long ex vivo culture is needed to generate enough cell numbers for transplantation. In the near future, combination of advanced biomaterials with cells from abundant outer sources will allow advances in the field. For the former, magnetically aligned collagen is one of the most promising ones. For the latter, different cell types will be optimal: 1) for epithelial replacement: oral mucosal epithelium, ear epidermis, or bone marrow- mesenchymal stem cells, 2) for stromal regeneration: adipose-derived stem cells and 3) for endothelial replacement, the possibility of in vitro directed differentiation of adipose-derived stem cells towards endothelial cells provides an exciting new approach.

Safety and efficacy of the multitargeted receptor kinase inhibitor pazopanib in the treatment of corneal neovascularization.

PURPOSE To evaluate the safety and efficacy of topical pazopanib in the treatment of corneal neovascularization (CNV). METHODS Twenty eyes of 20 patients with stable CNV were enrolled in a prospective, open label, noncomparative study and treated with topical pazopanib 0.5% for 3 weeks, and followed for 12 weeks. The primary endpoint was to determine the tolerability and safety of topical pazopanib in the treatment of CNV defined by the occurrence of ocular and systemic adverse events during the study. The secondary endpoint was to evaluate the effect of topical pazopanib on the reduction of (1) neovascular area (NA), defined as the area of the corneal vessels themselves, (2) invasion area (IA), defined as the fraction of the total cornea into which the vessels extend, (3) vessel length (VL), defined as the mean measurement of the extent of vessels from end to end, and (4) vessel caliber (VC), defined as the mean diameter of the corneal vessels. RESULTS There were no severe adverse events following the use of topical pazopanib. Compared with the baseline visit, NA and VL showed a statistically significant decrease at week 3 (P = 0.02 and 0.01, respectively); and NA, IA, and VL statistically significantly decreased at week 12 (P = 0.03, 0.04, and <0.01, respectively). Visual acuity maintained without changes after the 12 week follow-up. CONCLUSIONS This preliminary study suggests that topical treatment with pazopanib 0.5% is safe, well tolerated, and may have a role as an alternative for the treatment of CNV (ClinicalTrials.gov number, NCT01257750).