Joseph B. Ciolino

A drug-eluting contact lens.

PURPOSE To formulate and characterize a drug-eluting contact lens designed to provide extended, controlled release of a drug. METHODS Prototype contact lenses were created by coating PLGA (poly[lactic-co-glycolic acid]) films containing test compounds with pHEMA (poly[hydroxyethyl methacrylate]) by ultraviolet light polymerization. The films, containing encapsulated fluorescein or ciprofloxacin, were characterized by scanning electron microscopy. Release studies were conducted in phosphate-buffered saline at 37 degrees C with continuous shaking. Ciprofloxacin eluted from the contact lens was studied in an antimicrobial assay to verify antimicrobial effectiveness. RESULTS After a brief and minimal initial burst, the prototype contact lenses demonstrated controlled release of the molecules studied, with zero-order release kinetics under infinite sink conditions for over 4 weeks. The rate of drug release was controlled by changing either the ratio of drug to PLGA or the molecular mass of the PLGA used. Both the PLGA and the pHEMA affected release kinetics. Ciprofloxacin released from the contact lenses inhibited ciprofloxacin-sensitive Staphylococcus aureus at all time-points tested. CONCLUSIONS A prototype contact lens for sustained drug release consisting of a thin drug-PLGA film coated with pHEMA could be used as a platform for ocular drug delivery with widespread therapeutic applications.

Changes in the posterior cornea after laser in situ keratomileusis and photorefractive keratectomy

PURPOSE: To study the changes in posterior corneal elevation after laser in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK) using Scheimpflug topography with the Pentacam anterior segment imaging system (Oculus, Inc.). SETTING: Department of Ophthalmology, Albany Medical Center, and a private clinical practice, Albany, New York, USA. METHODS: In this prospective study, 121 consecutive myopic eyes (103 LASIK and 18 PRK) were evaluated preoperatively and postoperatively with the Pentacam to determine elevation changes in the posterior corneal surface. Changes in posterior elevation were calculated by comparing the best‐fit sphere preoperatively and postoperatively to a fixed reference sphere using the central 9.0 mm preoperative cornea. Statistical and graphic analyses were performed. RESULTS: The 103 LASIK eyes had a mean correction of −3.76 diopters (D) and a mean ablation depth of 62.1 μm. The mean estimated residual bed thickness (RBT) (329 μm) demonstrated a mean posterior displacement of 2.64 ± 4.95 μm. The 18 PRK eyes had a mean correction of −2.69 D and a mean ablation depth of 53.2 μm. The mean estimated RBT (464 μm) had a mean posterior displacement of −0.88 ± 4.64 μm. The difference in the mean posterior corneal displacement between the LASIK and the PRK eyes was not statistically significant (P>.05, Student t test). CONCLUSIONS: There was no statistically significant difference in posterior corneal displacement between the LASIK and PRK patients. The changes in PRK and LASIK eyes appeared to be within acceptable measurement variation. Contrary to previous reports, ectatic changes to the posterior corneal surface did not routinely occur after LASIK surgery.

Retention Of The Boston Keratoprosthesis Type 1: Multicenter Study Results

OBJECTIVE To report the retention rate of the Boston keratoprosthesis type 1 and to identify risk factors for keratoprosthesis loss. DESIGN Cohort study. PARTICIPANTS A total of 300 eyes of 300 patients who underwent implantation of the Boston keratoprosthesis type I device between January 2003 and July 2008 by 19 surgeons at 18 medical centers. METHODS Forms reporting preoperative, intraoperative, and postoperative parameters were prospectively collected and subsequently analyzed at a central data collection site. MAIN OUTCOME MEASURES Keratoprosthesis retention. RESULTS A total cumulative number of 422 life-years of device implantation are included in this analysis. The average duration of follow-up was 17.1 ± 14.8 months, with a range of 1 week to >6.1 years. Ninety-three percent of the 300 Boston keratoprosthesis implants were retained at their last follow-up, corresponding to a retention time of 396 patient-years or 1.42 years/keratoprosthesis. The probability of retention after 1 year and 2 years was 94% and 89%, respectively. During the study period, 21 (7%) eyes failed to retain the device; the reasons for keratoprosthesis loss include sterile keratolysis (9), fungal infections (8), dense retroprosthetic membranes (3), and bacterial endophthalmitis (1). Multivariate analysis demonstrated 3 independent risk factors for keratoprosthesis loss: autoimmune cause (hazard ratio [HR], 11.94; 95% confidence interval [CI], 3.31-43.11), ocular surface exposure requiring a concomitant tarsorrhaphy (HR, 3.43; 95% CI, 1.05-11.22), and number of prior failed penetrating keratoplasties (HR, 1.64; 95% CI, 1.18-2.28). CONCLUSIONS The Boston keratoprosthesis type 1 seems to be a viable option for eyes that are not candidates for penetrating keratoplasty (PK). Ocular surface disease due to an autoimmune cause demonstrated the lowest retention rate. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

The TFOS International Workshop on Contact Lens Discomfort: executive summary.

Contact lens discomfort (CLD) is a frequently experienced problem, with most estimates suggesting that up to half of contact lens wearers experience this problem with some frequency or magnitude. This condition impacts millions of contact lens wearers worldwide. Yet, there is a paucity of consensus and standardization in the scientific and clinical communities on the characterization of the condition, including the definition, classification, epidemiology, pathophysiology, diagnosis, management, influence of contact lens materials, designs and care, and the proper design of clinical trials. The Tear Film & Ocular Surface Society (TFOS), which is a nonprofit organization, has conducted two prior international, consensus building workshops, including the Dry Eye WorkShop (DEWS; available in the public domain at http://www.tearfilm.org/tearfilm-reports-dews-report.php) and the Meibomian Gland Dysfunction Workshop (MGD; available in the public domain at http://www.tearfilm.org/tearfilm-reports-mgdreport.php). To that end, TFOS initiated the process of conducting a similar workshop in January 2012—a process that took approximately 18 months to complete and included 79 experts in the field. These experts participated in one or more topical subcommittees, and were assigned with taking an evidence-based approach at evaluating CLD. Eight topical subcommittees were formed, with each generating a related report, all of which were circulated for presentation, review, and input of the entire workshop membership. The entire workshop originally is being published in this issue of IOVS, in English, with subsequent translations into numerous other languages. All of this information is intended to be available and accessible online, free of charge. This article is intended to serve as an Executive Summary of the eight subcommittee reports, and all information contained here was abstracted from the full reports.

Risk factors for the development of retroprosthetic membranes with Boston Keratoprosthesis type 1: multicenter study results

OBJECTIVE The purpose of this study was to identify possible risk factors for retroprosthetic membrane (RPM) development in a large, multicenter cohort of patients receiving a Boston type 1 keratoprosthesis. DESIGN Cohort study. PARTICIPANTS The final analysis included 265 eyes of 265 patients who underwent implantation of a Boston keratoprosthesis type I device between January 2003 and July 2008 by 1 of 19 surgeons at 18 medical centers. METHODS Forms reporting preoperative, intraoperative, and postoperative parameters were prospectively collected and subsequently analyzed at a central data collection site. MAIN OUTCOME MEASURES The primary outcome was the presence or absence of an RPM during the follow-up period. RESULTS The average age of patients was 63.3±19.1 years, 48.5% of the patients were female, and 52.5% of procedures were performed on the right eye. The mean follow-up time was 17.8±14.9 months. The majority (85.4%; n = 222) had undergone an average of 2.2±1.2 (range, 1-8) penetrating keratoplasties before keratoprosthesis implantation, and 38 eyes (14.6%) received a primary keratoprosthesis. The overall RPM formation rate was 31.7% (n = 84). The most significant risk factor for RPM development was infectious keratitis (as a surgical indication for keratoprosthesis surgery itself), resulting in a rate of RPM formation of 70.6%. As an independent risk factor, the hazard ratio (HR) of RPM development in these eyes was 3.20 (95% confidence interval, 1.66-6.17). Aniridia was also an independent risk factor for RPM development (HR, 3.13; 95% confidence interval, 1.10-8.89). CONCLUSIONS Formation of RPM is a common complication of keratoprosthesis surgery, occurring in approximately one-third of cases. Eyes at the highest risk of RPM development are those receiving corneal replacement for infectious keratitis and aniridia.

In vivo performance of a drug-eluting contact lens to treat glaucoma for a month

For nearly half a century, contact lenses have been proposed as a means of ocular drug delivery, but achieving controlled drug release has been a significant challenge. We have developed a drug-eluting contact lens designed for prolonged delivery of latanoprost for the treatment of glaucoma, the leading cause of irreversible blindness worldwide. Latanoprost-eluting contact lenses were created by encapsulating latanoprost-poly(lactic-co-glycolic acid) films in methafilcon by ultraviolet light polymerization. In vitro and in vivo studies showed an early burst of drug release followed by sustained release for one month. Contact lenses containing thicker drug-polymer films demonstrated released a greater amount of drug after the initial burst. In vivo, single contact lenses were able to achieve, for at least one month, latanoprost concentrations in the aqueous humor that were comparable to those achieved with topical latanoprost solution, the current first-line treatment for glaucoma. The lenses appeared safe in cell culture and animal studies. This contact lens design can potentially be used as a treatment for glaucoma and as a platform for other ocular drug delivery applications.

Long-term stability of the posterior cornea after laser in situ keratomileusis

PURPOSE: To study long‐term changes in posterior corneal elevation after laser in situ keratomileusis (LASIK) using Scheimpflug topography (Pentacam, Oculus, Inc.) in eyes 1 year after LASIK. SETTING: Department of Ophthalmology, Albany Medical Center, and a private practice, Albany, New York, USA. METHODS: One hundred two myopic eyes of 52 consecutive patients presenting for their 1‐year follow‐up were prospectively evaluated using the Pentacam to determine elevation changes to the posterior corneal surface between preoperative and 1‐year postoperative measurements. Changes in posterior elevation were performed by comparing the best‐fit sphere preoperatively and postoperatively with a fixed reference sphere determined by the central 9.0 mm preoperative cornea. Statistical and graphical analyses were performed. RESULTS: One hundred two post‐LASIK eyes (mean correction −4.33 diopters; mean ablation depth 68.70 μm; mean estimated residual bed thickness 327 μm) had a mean posterior displacement of −0.47 μm ± 3.48 (SD) (range −10.0 to +7 μm). The mean follow‐up period was 13.6 months (range 8.8 to 19.3 months). CONCLUSIONS: In this population, no patient had significant forward protrusion of the posterior corneal surface a mean of 14 months after LASIK. The posterior cornea in post‐LASIK myopic eyes was very stable. Contrary to results in previous studies, progressive changes to the posterior corneal surface did not routinely occur after LASIK performed within established parameters.

A Prototype Antifungal Contact Lens

PURPOSE To design a contact lens to treat and prevent fungal ocular infections. METHODS Curved contact lenses were created by encapsulating econazole-impregnated poly(lactic-co-glycolic) acid (PLGA) films in poly(hydroxyethyl methacrylate) (pHEMA) by ultraviolet photopolymerization. Release studies were conducted in phosphate-buffered saline at 37°C with continuous shaking. The contact lenses and their release media were tested in an antifungal assay against Candida albicans. Cross sections of the pre- and postrelease contact lenses were characterized by scanning electron microscopy and by Raman spectroscopy. RESULTS Econazole-eluting contact lenses provided extended antifungal activity against Candida albicans fungi. Fungicidal activity varied in duration and effectiveness depending on the mass of the econazole-PLGA film encapsulated in the contact lens. CONCLUSIONS An econazole-eluting contact lens could be used as a treatment for fungal ocular infections.

Contact lenses for drug delivery.

The majority of ocular medications are delivered to the eye topically, often in the form of a solution, or eye drop. Contact lenses could potentially also be used to deliver medications to the eye. Recently, progress has been made in developing a drug-eluting contact lens. Different designs have been proposed and several offer the hope of expanding the therapeutic armamentarium for eye care providers.

Cost-Effectiveness of the Boston Keratoprosthesis

PURPOSE To conduct a cost-utility analysis and determine the cost-effectiveness of the Boston Keratoprosthesis (Boston Kpro). DESIGN Retrospective cohort study. METHODS setting: The Massachusetts Eye and Ear Infirmary corneal service. patients: Inclusion required a minimum 2-year follow-up. Patients with autoimmune diseases and chemical burns were excluded. Eighty-two patients were included with various indications for surgery. intervention: The keratoprosthesis is a collar button-shaped polymethylmethacrylate (PMMA) device consisting of 2 curved plates sandwiched around a corneal donor (allo)graft. The device is assembled intraoperatively and sutured to a patients eye after removing the diseased cornea. MAIN OUTCOME MEASURES Average cost-effectiveness of the keratoprosthesis was determined by cost-utility analysis, using expected-value calculations and time-tradeoff utilities. The comparative effectiveness, or gain in quality-adjusted life years (QALYs), was also sought. Cost-effectiveness was compared to recently published data on penetrating keratoplasty (PK). RESULTS A total discounted incremental QALY gain for the Boston Kpro of 0.763 correlated with a conferred QALY gain of 20.3% for the average patient. The average cost-effectiveness of the keratoprosthesis was