Parag A. Majmudar

Phakic Intraocular Lens Implantation for the Correction of Myopia: A Report by the American Academy of Ophthalmology

OBJECTIVE To review the published literature for evaluation of the safety and outcomes of phakic intraocular lens (pIOL) implantation for the correction of myopia and myopic astigmatism. METHODS Literature searches of the PubMed and Cochrane Library databases were conducted on October 7, 2007, and July 14, 2008. The PubMed search was limited to the English language; the Cochrane Library was searched without language limitations. The searches retrieved 261 references. Of these, panel members chose 85 papers that they considered to be of high or medium clinical relevance to this assessment. The panel methodologist rated the articles according to the strength of evidence. RESULTS Two pIOLs have been approved by the US Food and Drug Administration (FDA): one iris-fixated pIOL and one posterior-chamber IOL. In FDA trials of iris-fixated pIOLs, uncorrected visual acuity (UCVA) was >or=20/40 in 84% and >or=20/20 in 31% after 3 years. In FDA trials of posterior-chamber pIOLs, UCVA was >or=20/40 in 81% and >or=20/20 in 41%. Satisfaction with the quality of vision with both types of pIOLs was generally high. Toric anterior- and posterior-chamber pIOLs have shown improved clinical results in European trials compared with spherical pIOLs. Comparative studies showed pIOLs to provide better best spectacle-corrected visual acuity (BSCVA) and refractive predictability and stability compared with LASIK and photorefractive keratectomy and to have a lower risk of retinal detachment compared with refractive lens exchange. Reported complications and long-term safety concerns include endothelial cell loss, cataract formation, secondary glaucoma (pupillary block, pigment dispersion), iris atrophy (pupil ovalization), and traumatic dislocation. CONCLUSIONS Phakic IOL implantation is effective in the correction of myopia and myopic astigmatism. In cases of high myopia of -8 diopters or more, pIOLs may provide a better visual outcome than keratorefractive surgeries and better safety than refractive lens exchange. The short-term rates of complications and loss of BSCVA are acceptable. Comprehensive preoperative evaluation and long-term postoperative follow-up examinations are needed to monitor for and prevent serious complications, and to establish long-term safety.

Wavefront-Guided LASIK for the Correction of Primary Myopia and Astigmatism A Report by the American Academy of Ophthalmology

OBJECTIVE To describe wavefront-guided (WFG) LASIK for the primary treatment of low to moderate levels of myopia and astigmatism and to examine the evidence on the safety and effectiveness of the procedure in comparison with conventional LASIK. METHODS Literature searches conducted in 2004, 2005, 2006, and 2007 retrieved 209 unique references from the PubMed and Cochrane Library databases. The panel selected 65 articles to review, and of these, chose 45 articles that they considered to be of sufficient clinical relevance to submit to the panel methodologist for review. During the review and preparation of this assessment, an additional 2 articles were included. A level I rating was assigned to properly conducted, well-designed, randomized clinical trials; a level II rating was assigned to well-designed cohort and case-controlled studies; and a level III rating was assigned to case series, case reports, and poorly designed prospective and retrospective studies. In addition, studies that were conducted by laser manufacturers before device approval (premarket approval) were reviewed as a separate category of evidence. RESULTS The assessment describes studies reporting results of WFG LASIK clinical trials, comparative trials, or both of WFG and conventional LASIK that were rated level II and level III. There were no studies rated as level I evidence. Four premarket approval studies conducted by 4 laser manufacturers were included in the assessment. The assessment did not compare study results or laser platforms because there were many variables, including the amount of follow-up, the use of different microkeratomes, and the level of preoperative myopia and astigmatism. CONCLUSIONS There is substantial level II and level III evidence that WFG LASIK is safe and effective for the correction of primary myopia or primary myopia and astigmatism and that there is a high level of patient satisfaction. Microkeratome and flap-related complications are not common but can occur with WFG LASIK, just as with conventional LASIK. The WFG procedure seems to have similar or better refractive accuracy and uncorrected visual acuity outcomes compared with conventional LASIK. Likewise, there is evidence of improved contrast sensitivity and fewer visual symptoms, such as glare and halos at night, compared with conventional LASIK. Even though the procedure is designed to measure and treat both lower- and higher-order aberrations (HOAs), the latter are generally increased after WFG LASIK. The reasons for the increase in HOA are likely multifactorial, but the increase typically is less than that induced by conventional LASIK. No long-term assessment of WFG LASIK was possible because of the relatively short follow-up (12 months or fewer) of most of the studies reviewed.

Effect of Mitomycin C on the Corneal Endothelium When Used for Corneal Subepithelial Haze Prophylaxis Following Photorefractive Keratectomy

PURPOSE To evaluate the potential effect of topical mitomycin C (MMC) on the corneal endothelium of myopic patients undergoing photorefractive keratectomy (PRK). METHODS Sixteen eyes with a planned ablation depth >75 microm underwent PRK followed by 0.02% MMC applied for 12 seconds using a methylcellulose sponge. Endothelial specular microscopy was performed with the Keeler-Konan specular photomicroscope in 16 eyes before and at least 1 year after surgery. Mean follow-up was 18 months (range: 12 to 24 months). Mean cell density, coefficient of variation of mean cell area, and percentage of hexagonal cells were measured and calculated using computerized morphometric analysis. RESULTS Mean endothelial cell densities before and after surgery were 2882 +/- 783 cells/mm2 (range: 1511 to 4022 cells/mm2) and 2867 +/- 588 cells/mm2 (range: 1638 to 3881 cells/mm2), respectively (P > .05). Mean coefficient of variation before and after surgery was 0.30 +/- 0.07 (range: 0.23 to 0.49) and 0.26 +/- 0.04 (range: 0.22 to 0.33), respectively (P=.06). Mean percentage of hexagonal cells before and after surgery was 61% +/- 6.8% (range: 47% to 70%) and 66% +/- 6.7% (range: 54% to 75%), respectively. CONCLUSIONS Administration of MMC for haze prophylaxis following PRK did not have a significant effect on quantitative endothelial cell density or qualitative morphometric parameters in this study.

How and when to use mitomycin-C in refractive surgery.

Purpose of review Mitomycin-C is an antimetabolite that has seen increased use in ophthalmology over the past several decades. From glaucoma surgery to the management of various corneal disorders, mitomycin-C seems to be a viable tool in the management of scar and haze formation. Recent findings With the constant evolution of refractive surgery, mitomycin-C has come to the forefront as a modulator of corneal wound healing after excimer laser surface ablation. Summary This article will describe the various indications, techniques, and current trends of mitomycin-C application in corneal refractive surgery.

Dysfunctional tear syndrome: dry eye disease and associated tear film disorders - new strategies for diagnosis and treatment.

Dysfunctional tear syndrome (DTS) is a common and complex condition affecting the ocular surface. The health and normal functioning of the ocular surface is dependent on a stable and sufficient tear film. Clinician awareness of conditions affecting the ocular surface has increased in recent years because of expanded research and the publication of diagnosis and treatment guidelines pertaining to disorders resulting in DTS, including the Delphi panel treatment recommendations for DTS (2006), the International Dry Eye Workshop (DEWS) (2007), the Meibomian Gland Dysfunction (MGD) Workshop (2011), and the updated Preferred Practice Pattern guidelines from the American Academy of Ophthalmology pertaining to dry eye and blepharitis (2013). Since the publication of the existing guidelines, new diagnostic techniques and treatment options that provide an opportunity for better management of patients have become available. Clinicians are now able to access a wealth of information that can help them obtain a differential diagnosis and treatment approach for patients presenting with DTS. This review provides a practical and directed approach to the diagnosis and treatment of patients with DTS, emphasizing treatment that is tailored to the specific disease subtype as well as the severity of the condition.

Relative strength of photodynamic biologic tissue glue in penetrating keratoplasty in cadaver eyes

Purpose: To compare the relative strength of photodynamic biologic tissue glue (PBTG) with that of 10‐0 nylon sutures in closing penetrating keratoplasty (PKP) wounds in cadaver eyes. Setting: Corneal Research Laboratory, University of Chicago, Chicago, Illinois, USA. Methods: A 7 mm central corneal trephination was performed on 8 recently enucleated human eyes. Each corneal button was removed and then resutured in its original position, using 4 interrupted 10‐0 nylon cardinal sutures and PBTG (n = 7) or 16 interrupted 10‐0 nylon sutures (n = 1). Wound leak and incisional bursting pressures were determined. Results: The average pressure at which wound leak and iris prolapse occurred was 124 mm Hg (range 70 to 180) and 185 mm Hg (range 90 to 300), respectively. The pressure required to create wound leak increased as the time between glue application and pressurization of the globe lengthened (mean 22 minutes, range 5 to 60 minutes), indicating that the bonding and stability of the adhesive increased with time. In contrast, the control eye developed wound leak at 70 mm Hg and iris prolapse at 300 mm Hg. Conclusions: Photodynamic biologic tissue glue was comparable to sutures in providing adequate corneal wound strength in PKP in a cadaver eye model. Wound closure with PBTG may reduce the number of sutures required in corneal transplantation and decrease the incidence of suture‐related complications and allograft rejection.

Safety of Lifitegrast Ophthalmic Solution 5.0% in Patients With Dry Eye Disease: A 1-Year, Multicenter, Randomized, Placebo-Controlled Study.

Purpose: To evaluate the 1-year safety of lifitegrast ophthalmic solution 5.0% in patients with dry eye disease compared with placebo. Methods: SONATA (Safety Of a 5.0% coNcentrATion of lifitegrAst ophthalmic solution) was a multicenter, randomized, prospective, double-masked, placebo-controlled phase 3 study (NCT01636206). Adults (≥18 years) with dry eye disease (Schirmer test score ≥1 and ⩽10 mm; corneal staining score ≥2.0) were randomized 2:1 to lifitegrast ophthalmic solution 5.0% or placebo twice daily for 360 days. The primary objective was percentage and severity of treatment-emergent adverse events (TEAEs). Secondary objectives were ocular safety measures: corneal fluorescein staining, drop comfort, best-corrected visual acuity, slit-lamp biomicroscopy, and intraocular pressure over 7 visits. Exploratory objectives included concentration of lifitegrast in plasma. Results: The safety population comprised 331 participants (220 lifitegrast; 111 placebo). There were no serious ocular TEAEs. Overall, 53.6% of participants receiving lifitegrast experienced ≥1 ocular TEAE versus 34.2% in the placebo group; most TEAEs were mild to moderate in severity. Rates of discontinuation because of TEAEs were 12.3% (lifitegrast) versus 9.0% (placebo). The most common (>5%) TEAEs occurring in either treatment group were instillation site irritation (burning), instillation site reaction, visual acuity reduced, dry eye, and dysgeusia (change in taste). Ocular safety parameters for lifitegrast were similar to placebo. The mean plasma lifitegrast concentration at 360 days (n = 43) was below the limit of detection. There was no indication of systemic toxicity or localized infectious complications secondary to chronic immunosuppression. Conclusions: Lifitegrast ophthalmic solution 5.0% seemed safe and well tolerated in this study, with no unexpected adverse events.

Hydrogel sealant versus sutures to prevent fluid egress after cataract surgery

Purpose To evaluate the effectiveness of a hydrogel sealant versus a suture in preventing fluid egress after wound leakage in cataract surgery. Setting Twenty‐four ophthalmic clinical practices in the United States. Design Prospective randomized parallel‐arm controlled multicenter subject‐masked study. Methods Healthy patients having uneventful clear corneal incision (CCI) cataract surgery were eligible for the study. Spontaneous and provoked fluid egress from wounds was evaluated at the time of surgery using a calibrated force gauge. Eyes with leakage were randomized to receive a hydrogel sealant (Resure) or a nylon suture at the main incision site. Incision leakage was reevaluated 1, 3, 7, and 28 days postoperatively. Results Of 500 eyes, 488 had leakage at the time of cataract surgery. The leak was spontaneous in 244 cases (48.8%), and 488 (97.6%) of all incisions leaked with 1.0 ounce or less of applied force. After randomization, 12 (4.1%) of 295 eyes in the sealant group and 60 (34.1%) of 176 eyes in the suture group had wound leakage with provocation (P<.0001). The overall incidence of adverse ocular events was statistically significantly lower in the sealant group than in the suture group (P<.05). Conclusions In this study, 97.6% of CCIs leaked after cataract surgery. The hydrogel sealant was safe and effective and better than a suture for the intraoperative management of CCIs with leakage as seen on Seidel testing and for the prevention of postoperative fluid egress. Financial Disclosure Proprietary or commercial disclosures are listed after the references.

Sustained-release dexamethasone for the treatment of ocular inflammation and pain after cataract surgery.

Purpose To evaluate the safety and efficacy of dexamethasone as a sustained‐release drug depot when placed in the canaliculus for the treatment of ocular inflammation and pain in cataract surgery patients. Setting Four private practice sites in the United States. Design Multicenter randomized double‐masked clinical trial. Methods Patients were randomized (1:1) to receive either the sustained‐release dexamethasone or a placebo vehicle punctum plug inserted into the inferior distal canaliculus of the operated eye intraoperatively during cataract surgery. The primary endpoints were the proportions of patients with absence of cells or pain in the anterior chamber at 8 days. Secondary endpoints included cells, flare, pain, and the presence of the device at various timepoints through 30 days. Results Approximately one fifth (20.7%) of patients in the sustained‐release dexamethasone group had an absence of anterior chamber cells at 8 days compared with 10.0% in the placebo group (P = .1495). A higher proportion of patients in the sustained‐release dexamethasone group (79.3%) than in the placebo group (30.0%) had an absence of ocular pain at 8 days (P < .0001) and at all other timepoints (P < .0002). There were significantly higher proportions of patients in the sustained‐release dexamethasone group than in the placebo group with an absence of anterior chamber cells, anterior chamber flare, and pain at several timepoints through 30 days (P ≤ .0251). Conclusion Sustained‐release dexamethasone provided elution of drug for up to 1 month after cataract surgery, providing clinically significant reductions in inflammation and pain. Financial Disclosure Dr. Masket is a consultant to and shareholder in Ocular Therapeutix, Inc. No other author has a financial or proprietary interest in any material or method mentioned.

Elestat (epinastine HCl ophthalmic solution 0.05%) as a therapeutic for allergic conjunctivitis

Epinastine 0.05% ophthalmic solution (Elestat, Inspire Pharmaceuticals Inc, Durham, NC) is the most recently approved topical therapy for ocular allergies, having been available in the US market since February 2004. It is indicated for the prevention of itching associated with allergic conjunctivitis and is approved for twice-daily dosing. This article reviews the impact of allergic conjunctivitis and its pathophysiology, the mechanism of action of epinastine, and clinical attributes of topical ophthalmic epinastine including its efficacy, safety, and impact on the ocular surface.