Design and Biocompatibility of a Novel, Flexible Artificial Cornea.

Purpose: We sought to introduce the materials, design, and biocompatibility of a flexible and suturable artificial corneal device. Methods: Single-piece, fully synthetic, optic-skirt design devices were made from compact perfluoroalkoxy alkane. The skirt and the optic wall surfaces were lined with a porous tissue ingrowth material using expanded polytetrafluoroethylene. Full-thickness macroapertures around the skirt perimeter were placed to facilitate nutrition of the recipient cornea. Material properties including the skirt's modulus of elasticity and bending stiffness, optic light transmission, wetting behavior, topical drug penetrance, and degradation profile were evaluated. Results: The final prototype suitable for human use has a transparent optic with a diameter of 4.60 mm anteriorly, 4.28 mm posteriorly, and a skirt outer diameter of 6.8 mm. The biomechanical and optical properties of the device closely align with the native human cornea with an average normalized device skirt-bending stiffness of 4.7 kPa·mm4 and light transmission in the visible spectrum ranging between 92% and 96%. No optical damage was seen in the 36 devices tested in fouling experiments. No significant difference was observed in topical drug penetrance into the anterior chamber of the device implanted eye compared with the naïve rabbit eye. Conclusions: The flexibility and biocompatibility of our artificial cornea device may offer enhanced tissue integration and decreased inflammation, leading to improved retention compared with rigid keratoprosthesis designs. Translational Relevance: We have developed a fully synthetic, flexible, suturable, optic-skirt design prototype artificial cornea that is ready to be tested in early human feasibility studies.

Demographic and Psychiatric Associations With Dry Eye in a Medicare Population.

PURPOSE: The purpose of this study was to investigate the impact of demographic characteristics and psychiatric comorbidity on the prevalence of dry eye disease in the American geriatric population. METHODS: Data were collected from a 2011 nationwide sample of Medicare beneficiaries aged 65 years and older (N = 1,321,000). Age, sex, race/ethnicity, residential area, climate region, and income, along with psychiatric comorbidities including depression and anxiety, were collected. Multivariable logistic regression models were used to assess the relationship between demographic and psychiatric factors and the prevalence of dry eye disease. RESULTS: Among 21,059 patients with clinically significant dry eye, women had higher odds of having dry eye compared with men [odds ratio (OR) 2.03, 95% confidence interval (1.97-2.10)]. Asian and Native American patients had increased odds of having dry eye compared with White patients [OR 1.85 (1.69-2.02) and OR 1.51 (1.19-1.93)], while Black patients were less likely to have dry eye [OR 0.83 (0.79-0.87)]. Patients aged 75 to 84 years and 85+ were more likely to have dry eye compared with those aged 65 to 74 years [OR 1.49 (0.45-1.53) and OR 1.54 (1.48-1.60)]. Having both depression and anxiety were associated with higher odds of having dry eye [OR 2.38 (2.22-2.55)] compared with having depression alone [OR 1.95 (1.86-2.04)] or anxiety alone [OR 2.22 (2.10-2.35)]. CONCLUSIONS: Significant racial and regional disparities in dry eye prevalence were found. Psychiatric association with dry eye varied with age, sex, race, and residence region. Further research is needed to comprehend the underlying mechanisms, implications, and to address disparities in the diagnosis and management of dry eye.

Cornea Classic: "Grading of Corneal and Conjunctival Staining in the Context of Other Dry Eye Tests," Bron, Evans, and Smith, 2003.

ABSTRACT: Dry eye is an increasingly common ocular condition with significant impact on quality of life due to eye discomfort and blurred vision complaints. In addition, the financial burden of dry eye on both patients and society is substantial. Although there has been a recent explosion of research in the field since 2002 with the approval of the first prescription topical treatment (Restasis, Allergan Inc, Irvine CA), dry eye lags behind other ophthalmic conditions where clinically meaningful outcome measures are closely tied with the metrics by which their therapeutics are evaluated. Unfortunately, current practice is such that physicians largely rely on patient symptoms to evaluate dry eye, and these do not always correlate with objective ocular surface and tear film parameters. In patients with severe dry eye, the patient-reported symptoms are likely dampened because of the neurotrophic state of the ocular surface, which accompanies any long-standing inflammatory ocular condition. Therefore, staining of the corneal and conjunctival surface using vital dyes is an invaluable dry eye test to provide information normally not visible during routine slit-lamp examination. The landmark article by Bron, Evans, and Smith published in Cornea in 2003 provides excellent guidance to clinicians to highlight and quantify ocular surface parameters in patients with dry eye. Validation studies correlating conjunctival or corneal staining with tangible quality-of-life parameters and metrics to measure those are needed to verify ocular surface staining as a clinically meaningful dry eye outcome to be used in clinical practice and clinical trials.

Twelve-Month Clinical and Histopathological Performance of a Novel Synthetic Cornea Device in Rabbit Model.

Purpose: To report the biological stability and postoperative outcomes of a second-generation, single-piece, flexible synthetic cornea in a rabbit model. Methods: Device materials and design were amended to enhance biointegration. Optic skirt design devices were made from compact perfluoroalkoxy alkane with porous expanded polytetrafluoroethylene ingrowth surface overlying the skirt and optic wall. Sixteen devices were implanted into intrastromal pocket in rabbit eyes. Rabbits were randomly assigned to 6- and 12-month follow-up cohorts (n = 8 in each) postoperatively. Monthly examinations and optical coherence tomography assessed cornea-device integration, iridocorneal angle, optic nerve, and retina. Results: There were no intraoperative complications. All devices were in situ at exit, with clear optics. No retroprosthetic membrane, glaucoma, cataract formation, or retinal detachment was observed. Two rabbits in the 6-month group had mild, focal anterior lamella thinning without retraction adjacent to the optic near tight sutures. Three postoperative complications occurred in the 12-month group. One rabbit diagnosed with endophthalmitis was euthanized on day 228. Mild sterile focal retraction of anterior lamella occurred in two rabbits, which were terminated on days 225 and 315. Light microscopic examination of enucleated globes demonstrated fibroplasia with new collagen deposition into the porous scaffold without significant inflammation, encapsulation, or granuloma formation. Conclusions: Clinical evaluations, imaging, and histopathological findings indicate favorable outcomes of this synthetic corneal device in a rabbit model. Early feasibility studies in humans are being planned. Translational Relevance: Favorable 12-month results of the device in rabbits demonstrate vision-restoring potential in corneally blind individuals at high risk of failure with donor keratoplasty.

Glaucoma and Ocular Surface Disease: More than Meets the Eye.

Understanding the association between ocular surface disease and glaucoma is important for improving adherence to treatment and introducing practical solutions. While topical antihypertensive medications for glaucoma are well tolerated according to short-term studies, there is little evidence on their long-term effects. Since they are often required for many years, the effects of these drops on the ocular surface become important in regard to quality of life and adherence. In this nonsystematic review performed in April 2022, we summarize what is known about the relationship between glaucoma and ocular surface disease. Specifically, we examine how each class of topical glaucoma drops affects the ocular surface. We then review the treatment of ocular surface disease for patients on topical glaucoma therapy. Finally, we discuss treatments that may reduce or eliminate the burden of topical medications.

Trends in Early Graft Failure Leading to Regrafting After Endothelial Keratoplasty in the United States.

PURPOSE: The purpose of this study was to report trends in the prevalence of early graft failure after endothelial keratoplasty in the United States. METHODS: Descemet membrane endothelial keratoplasty (DMEK) and Descemet stripping automated endothelial keratoplasty (DSAEK) graft volumes were collected from records maintained by 6 major eye banks in the United States from January 1, 2013, to December 31, 2018. The prevalence and presumed cause of early graft failures (defined as a graft with persistent edema or regrafted within 8 weeks after keratoplasty) each year were sourced from surgeon-reported adverse events. Failed graft cases from the 3 eye banks were compared with nonfailures at the donor and recipient levels to perform subset analysis of factors associated with early graft failure. RESULTS: A total of 51,887 endothelial keratoplasty tissues were distributed during the study period; 72% were DSAEK grafts. The total number of early graft failures reported was 168 of 14,284 (1.18%) for DMEK and 322 of 37,603 (0.86%) for DSAEK. Early DMEK failures decreased from 2013 (7.69%) to 2018 (0.68%). In generalized linear mixed model analyses adjusting for donor tissue characteristics, recipient age, and diagnosis, an association of borderline significance was found between higher donor age and early failure [odds ratio (95% confidence interval): 1.03 (1.00-1.05); unit change of 1 yr] and DSAEK [odds ratio 1.02 (1.00-1.04); unit of change 1 yr] cases. CONCLUSIONS: The proportion of early graft failures in DMEK decreased over time and was comparable with failure rates in DSAEK at the end of the study period. The surgical learning curve might have played a role.

Immunopathological Features of Severe Chronic Atopic Keratoconjunctivitis and Effects of Topical Cyclosporine Treatment.

PURPOSE: To assess differential roles of inflammatory cells in pathophysiology of severe atopic keratoconjunctivitis (AKC) and evaluate immunomodulatory effects of topical cyclosporine A (CsA). METHODS: A total of 10 patients with severe, steroid-dependent/resistant chronic active AKC were treated using frequent topical CsA 0.05% as monotherapy for 2 months. Conjunctival biopsy specimens before and after treatment were examined using immunohistochemistry. A total of 10 healthy age-matched adults served as the control group. RESULTS: Baseline AKC samples revealed greater cluster of differentiation 4 (CD4), interferon gamma (IFNγ), human leukocyte antigen-D-related (HLA-DR) positive cell densities compared with healthy controls (P < 0.05), as well as interleukin (IL)-17 (P = 0.08). Topical CsA treatment induced a significant reduction in CD4 and IL-17 expressions (P < 0.05); post-treatment levels were same as normals (P > 0.05). Despite reduction after treatment (P = 0.06), HLA-DR expression remained higher than controls (P < 0.05). CONCLUSIONS: AKC-related conjunctival inflammation appears to be mediated by delayed hypersensitivity. In this short-term trial, frequent topical CsA improved conjunctival inflammation.

Frequent Dosing of Topical Cyclosporine A for Severe Ocular Surface Disease.

PURPOSE: To study the systemic safety and patient tolerability of frequent dosing of cyclosporine A (CsA) 0.05% eyedrops in the treatment of ocular surface disease. This is a retrospective case series. Patients with significant ocular surface diseases who were treated using topical CsA higher than the usual twice daily dosing (3-8 times daily and over a treatment period of 1-70 months). The main outcome measures are plasma levels of CsA and local tolerability. METHODS: Symptom assessment, corneal staining using fluorescein, conjunctival staining using lissamine green, tear film breakup time, and other signs according to the disease process were monitored. Discontinuation of treatment due to intolerability was recorded. CsA levels were measured in the plasma at a clinical laboratory. RESULTS: Plasma levels of CsA were below the level of detection (7 ng/mL) in all the 41 patients included. All patients tolerated the treatment well with none discontinuing due to any treatment-related local adverse effects. CONCLUSIONS: This study demonstrates that CsA 0.05% ophthalmic emulsion applied more frequently than the usual twice daily dosing was safe and well tolerated in patients with significant ocular surface diseases.

Boston Type 1 Keratoprosthesis versus Repeat Donor Keratoplasty for Corneal Graft Failure: A Systematic Review and Meta-analysis.

PURPOSE: To compare repeat penetrating keratoplasty (PK) with Boston type I keratoprosthesis (KPro) implantation for full-thickness donor corneal graft failure. DESIGN: Previous donor graft failure is a common indication for both PK and KPro implantation. Selection of the surgical procedure is entirely dependent on the surgeon because there are no studies available for guidance. Therefore, a systematic review was undertaken to examine vision, device retention, graft clarity, and postoperative glaucoma and infection outcomes after repeat PK versus KPro implantation. METHODS: Articles with data regarding repeat PK published between 1990 and 2014 were identified in PubMed, EMBASE, the Latin American and Caribbean Health Sciences Literature Database, and the Cochrane Central Register of Controlled Trials and were reviewed. Results were compared with a retrospective review of consecutive, nonrandomized, longitudinal case series of KPro implantations performed at 5 tertiary care centers in the United States. Visual acuity at 2 years was the primary outcome measure. The proportion of clear grafts in the repeat PK group, device retention in the KPro group, and the development of postoperative glaucoma and infection were secondary outcome measures. RESULTS: The search strategy identified 17 128 articles in the PK analysis. After screening, 26 studies (21 case series and 5 cohort studies) were included in the review. Pooled analysis of the 26 unique studies demonstrated a 42% (95% confidence interval [CI], 30%-56%) likelihood of maintaining 20/200 or better at 2 years after repeat PK, compared with an 80% (95% CI, 68%-88%) probability with KPro implantation. The probability of maintaining a clear graft at 5 years was 47% (95% CI, 40%-54%) after repeat PK, whereas the probability of retention of the KPro at 5 years was 75% (95% CI, 64%-84%). The rate of progression of glaucoma at 3 years was 25% (95% CI, 10%-44%) after repeat PK and 30% in the KPro cohort. CONCLUSIONS: These results demonstrate favorable outcomes of KPro surgery for donor corneal graft failure with a greater likelihood of maintaining visual improvement without higher risk of postoperative glaucoma compared with repeat donor PK.

The Usage of a Conjunctival Flap to Improve Retention of Boston Type 1 Keratoprosthesis in Severe Ocular Surface Disease.

PURPOSE: The Boston keratoprostheses type 1 devices (KPro) are utilized in cases unfavorable to penetrating keratoplasty. The prognosis remains guarded in cases of ocular surface disease due to risk of tissue necrosis. We describe a novel surgical approach using a conjunctival flap with a delayed opening to improve retention. METHODS: In three patients with advanced cicatrizing conjunctivitis, a Type 1 keratoprosthesis was stabilized using a full tarsal conjunctival flap. Three months postoperatively, an opening was created in the flap overlying the optical portion of the device. RESULTS: All patients had no device related complications over a mean follow-up period of 17.7 months (range 15-21 months) and vision remained excellent at better than 20/200 for all patients. CONCLUSIONS: Utilization of a tarsal flap either primarily as part of a two stage modified technique or secondarily in cases of tissue necrosis and impending device extrusion might maximize retention of the type 1 KPro.

Outcomes of Repeat Boston Type 1 Keratoprosthesis Implantation.

PURPOSE: To describe the outcomes and prognostic characteristics of patients who had a repeat Boston type 1 keratoprosthesis (KPro) implantation. DESIGN: Retrospective case series. METHODS: setting: Data regarding preoperative clinical and demographic characteristics and postoperative course during initial and repeat KPro placement were collected at multiple centers across the country. PATIENTS: Forty-eight eyes underwent explantation of KPro owing to complications between September 2003 and August 2014 at 5 participating tertiary eye care centers in the United States. Of those, 36 eyes that received a subsequent replacement device were included. MAIN OUTCOME MEASURES: Visual acuity (VA) outcomes and postoperative complications. RESULTS: Ocular surface disease was significantly more common in eyes that required a device explantation, compared to those that retained the device (P < .001). Sixty-seven percent of eyes (24/36) achieved VA ≥ 20/200 vision after the repeat KPro. The probability of these 24 eyes maintaining VA ≥ 20/200 after the repeat KPro was 87% at 1 year and 75% at 2 years. Predictors of the ability to maintain vision ≥ 20/200 following surgery were a better last-recorded vision before explantation (P = .0002) and better vision immediately after repeat KPro (P < .001). CONCLUSION: Ocular surface disease and its complications were associated with more frequent device removal. In these patients, repeat KPro resulted in restoration of vision. A reasonable visual acuity prior to device removal was associated with favorable long-term postoperative visual acuity and retention.

Ocular and systemic morbidity in a longitudinal cohort of Sjögren's syndrome.

PURPOSE: To report vision-threatening ocular manifestations of primary Sjögren's syndrome (SS). DESIGN: Retrospective review. PARTICIPANTS: Consecutive patients evaluated at an SS center between January 2007 and May 2011. METHODS: Data collection was completed in March 2013. The 2002 American-European consensus criteria were used for diagnosis of SS. MAIN OUTCOME MEASURES: Frequency of extraglandular ocular findings and timing of their diagnosis relative to that of SS and dry eye were assessed. RESULTS: One hundred sixty-three patients were included. Almost all patients (98%) had a history of dry eye for an average of 10.4 years (median, 7.9 years) before presentation. One or more extraglandular ocular manifestations were present in 40 patients (25%), and vision-threatening findings were present in 22 patients (13%). Twelve patients (55%) with a vision-threatening ocular finding did not have a diagnosis of SS at presentation. Sixty-eight patients (42%) had extraglandular systemic manifestations of SS. Patients with vision-threatening ocular findings were 3.9 times more likely to have systemic involvement (95% confidence interval, 1.4-11.0; P = 0.010). Peripheral neuropathy, interstitial nephritis, and vasculitis were more common in those with vision-threatening ocular findings compared with patients without (P < 0.05 for all). CONCLUSIONS: These results from a tertiary referral-based cohort demonstrate that primary SS frequently is associated with ocular and systemic complications. Dry eye precedes these findings on average by 1 decade. Therefore, ophthalmologists should consider assessing for SS in patients with clinically significant dry eye.

Dry eye: an inflammatory ocular disease.

Keratoconjunctivitis sicca, or dry eye, is a common ocular disease prompting millions of individuals to seek ophthalmological care. Regardless of the underlying etiology, dry eye has been shown to be associated with abnormalities in the pre-corneal tear film and subsequent inflammatory changes in the entire ocular surface including the adnexa, conjunctiva and cornea. Since the recognition of the role of inflammation in dry eye, a number of novel treatments have been investigated designed to inhibit various inflammatory pathways. Current medications that are used, including cyclosporine A, corticosteroids, tacrolimus, tetracycline derivatives and autologous serum, have been effective for management of dry eye and lead to measurable clinical improvement.

Long-term outcomes of boston type 1 keratoprosthesis implantation: a retrospective multicenter cohort.

PURPOSE: To study the long-term outcomes of Boston type 1 keratoprosthesis (KPro) surgery. DESIGN: Retrospective, multicenter case series. PARTICIPANTS: A total of 158 eyes of 150 patients underwent KPro implantation at 5 participating tertiary centers in the United States between January 2003 and December 2006. Of those, 139 eyes of 133 patients were included in the analyses. METHODS: The medical records of consecutive adult patients who received KPro surgery were reviewed. All patients with at least 1 postoperative visit were retained in the outcomes analyses. In eyes in which a repeat KPro procedure was performed, only the outcomes of the initial surgery were analyzed. MAIN OUTCOME MEASURES: Visual acuity (VA) outcomes, postoperative complications, and device retention. RESULTS: The mean follow-up was 46.7 ± 26 months with all but 4 eyes having at least 6 months of follow-up. Preoperatively, only 10.8% of the eyes had VA of ≥ 20/200. Postoperatively, the VA in 70% of eyes improved to ≥ 20/200. The probability of maintaining VA of ≥ 20/200 at 7 years was 50%. The device retention rate was estimated at 67% at 7 years. The 7-year cumulative incidence of complications was 49.7% for retroprosthetic membrane formation, 21.6% for glaucoma surgery, 18.6% for retinal detachment, and 15.5% for endophthalmitis. CONCLUSIONS: Although the risk for complications with longer follow-up seemed to increase, this large multicenter cohort demonstrates favorable outcomes with KPro, with a large number of patients achieving and retaining useful vision over a 7-year period.

Topical calcineurin inhibitors in the treatment of steroid-dependent atopic keratoconjunctivitis.

PURPOSE: To evaluate the long-term effectiveness of the combination of topical cyclosporine drops and tacrolimus ointment in the treatment of steroid-dependent atopic keratoconjunctivitis (AKC). METHODS: Ten patients with moderate to severe AKC participated in the study. Topical cyclosporine 0.05% was used, as a monotherapy, 6 times daily during the first month of the study, followed by 4 times daily during the second month. The patients were then instructed to self-treat with topical cyclosporine at a dose ranging from 2 to 6 times daily depending on the severity of the disease. Tacrolimus ointment 0.03% was applied on the lid skin. Follow-up examinations were performed approximately every 3 months. Each patient completed a follow-up period of at least 12 months. Symptoms and signs of AKC were assessed on the day of enrollment, on days 28, 56, and 63, and at subsequent follow-up visits. Flare-ups of AKC requiring steroid use and progression of the disease findings were also recorded. RESULTS: All patients experienced significant improvement of their symptoms and signs during the first 2 months of the study. Two patients were lost to follow-up after the initial 2 months. One patient was noncompliant and continued the treatment only for 7 months. During the median treatment period of 21.5 months for the 7 continuing patients, a total of only 2 flare-up episodes were noted requiring topical steroids. CONCLUSIONS: Adequate topical immunomodulation using topical calcineurin inhibitors may eliminate the need for steroids and favorably alter the long-term prognosis of patients with AKC.

Visual and clinical outcomes of explantation versus preservation of the intraocular lens during keratoprosthesis implantation.

PURPOSE: To compare the short-term visual and clinical outcomes of explantation versus preservation of a posterior chamber intraocular lens (PC IOL) during keratoprosthesis implantation. SETTING: Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, USA. DESIGN: Comparative case series. METHODS: This study comprised patients who had implantation of an aphakic or a pseudophakic Boston type I keratoprosthesis based on their lenticular status. Only adult patients who were pseudophakic with a PC IOL at the time of surgery and who had at least 1 year of follow-up were included. The postoperative refractive error, uncorrected and corrected visual acuities, and intraoperative and postoperative complications were analyzed. RESULTS: Fifteen patients with an unstable PC IOL had aphakic keratoprosthesis implantation with IOL explantation, and 10 patients had implantation of a pseudophakic keratoprosthesis. The postoperative best-ever visual acuity and magnitude of visual acuity improvement were comparable in the 2 groups. The mean postoperative spherical equivalent refractive error was significantly better in the aphakic group (-0.66 diopter [D] ± 1.59 [SD]) than in the pseudophakic group (-3.25 ± 3.20 D) (P=.04). The rate of postoperative complications in the 2 groups was low (P>.05). CONCLUSIONS: In this small short-term study, refractive outcomes were better in aphakic patients than in patients who were left pseudophakic. Although not frequent, posterior segment complications after IOL explantation might necessitate further surgeries and cause decreased visual acuity during long-term follow-up in the aphakic group.

Treatment of Sjögren's syndrome-associated dry eye an evidence-based review.

BACKGROUND: Outcomes-based review of reported treatment options for patients with dry eye secondary to Sjögren's syndrome (SS). CLINICAL RELEVANCE: Dry eye affects many individuals worldwide. Significant proportion of patients with dry eye has underlying SS, a progressive autoimmune condition. The few suggested guidelines for the treatment of dry eye are mostly based on severity of symptoms and/or clinical findings rather than on outcomes analysis, and do not differentiate SS from other causes of dry eye. METHODS AND LITERATURE REVIEW: A search strategy was developed to identify prospective, interventional studies of treatments for SS-associated dry eye from electronic databases. Eligible references were restricted to English-language articles published after 1975. These sources were augmented by hand searches of reference lists from accessed articles. Study selection, data extraction, and grading of evidence were completed independently by ≥4 review authors. RESULTS: The searches identified 3559 references as of August 10, 2010. After duplicate review of the titles and abstracts, 245 full-text papers were assessed, 62 of which were relevant for inclusion in the review. CONCLUSIONS: In the current literature on SS-associated dry eye, there is a paucity of rigorous clinical trials to support therapy recommendations. Nonetheless, the recommended treatments include topical lubricants, topical anti-inflammatory therapy, and tear-conserving strategies. The efficacy of oral secretagogues seems greater in the treatment of oral dryness than ocular dryness. Although oral hydroxychloroquine is commonly prescribed to patients with SS to alleviate fatigue and arthralgias, the literature lacks strong evidence for the efficacy of this treatment for dry eye.

Lamellar keratoplasty using gamma-irradiated corneal lenticules.

PURPOSE: To report the clinical outcomes of lamellar keratoplasty using sterile, gamma-irradiated corneal tissues (VisionGraft) for partial-thickness corneal defects. DESIGN: Interventional case series. METHODS: The medical records of 10 patients with partial-thickness corneal defects who were operated at The Wilmer Eye Institute between April 2009 and December 2009 were retrospectively reviewed. Indications for surgery included corneal melt with microperforation (n = 6), keratoprosthesis-associated corneal melt (n = 2), and noninflammatory limbal lesions (n = 2). The grafts were fashioned from full- or partial-thickness tissues using disposable trephines, based on the depth, shape, and size of the defect in the recipient bed, and were secured with multiple interrupted 10/0 nylon sutures. Rate of epithelialization and clarity of the grafts at the last visit were assessed retrospectively. RESULTS: All but 1 graft became epithelialized between postoperative 1st and 13th days. Corneal inflammation progressed in the 1 patient with Boston type 1 keratoprosthesis-associated corneal melt, probably attributable to the progression of underlying Sjögren syndrome, despite initiation of systemic immunomodulatory treatment, and required replacement of the device. The donor tissues remained clear in all the other cases over a period of 7 to 15 months. No immune rejection, infection, significant opacification, or neovascularization of the donor tissues were noted during a follow-up period. CONCLUSIONS: VisionGraft may be considered in lieu of fresh donor corneas for lamellar corneal patch grafts because of its availability, easy handling, and lack of immunogenicity.

Ocular surface distribution and pharmacokinetics of a novel ophthalmic 1% azithromycin formulation.

PURPOSE: To investigate the ocular distribution of 1% azithromycin ophthalmic solution and the effect of polycarbophil-based mucoadhesive formulation on ocular tissue levels of azithromycin after single and multiple topical administrations in the rabbit eye. METHODS: Rabbits were treated with either a single administration of 1% azithromycin solution with or without polycarbophil, or with multiple administrations of 1% azithromycin solution in polycarbophil. Drug concentrations were measured using LC/MS/MS. Conjunctiva, cornea, aqueous humor, and tear samples were analyzed over a period of 144 h after a single administration of azithromycin with or without polycarbophil. Eyelid, conjunctiva, cornea, aqueous humor, and tear samples were collected over a period of 288 h during and after multiple administrations of azithromycin. RESULTS: Azithromycin was rapidly absorbed and distributed in the ocular tissues, reaching within 5 min, concentrations of 10,539 microg/mL in tear film, 108 microg/g in conjunctiva, and 40 microg/g in the cornea. The drug demonstrated tissue-specific half-lives of 15, 63, and 67 h, respectively. Following multiple administrations, the drug gradually accumulated. The polycarbophil formulation increased the bioavailability of the drug, producing peak concentrations that were between 5- and 12-fold higher than those without polycarbophil. Azithromycin also distributed rapidly in the eyelids, reaching peak concentrations of 180 mug/g at the end of the 7-day treatment, and was eliminated with a half-life of 125 h. Six days after treatment was discontinued, eyelid levels of azithromycin were above 40 microg/g. CONCLUSIONS: Sustained and high concentrations were encountered with 7-day approved administration of 1% azithromycin formulation (AzaSite, Inspire Pharmaceuticals, Inc., Durham, NC) within all ocular surface tissues, particularly the lids. Many ocular surface disorders involving the tear film, eyelids, and adnexal structures are associated with chronic, low-grade bacterial infection and may potentially lead to decreased vision secondary to corneal scarring. Various topical antibiotic and steroid combinations with or without oral tetracyclines are commonly used with variable clinical response and known potential side effects. The clinical relevance of this study is unknown; however, the long-lasting antibacterial and additional anti-inflammatory properties of topical azithromycin might offer an effective alternative treatment option and should be explored further in clinical studies.