Gary N. Foulks

Meibomian Gland Dysfunction: A Clinical Scheme for Description, Diagnosis, Classification, and Grading

Although meibomian gland disease (MGD) is one of the most common disorders encountered in ophthalmic practice, there has been no descriptive system consistently accepted to clinically characterize the anatomical and correlative biochemical alterations that occur in this condition. The purpose of this review is to synthesize a clinical description of meibomian gland disease and to provide a scheme for diagnosis, classification, and quantification that will be of value in the clinical setting and in the conduct of clinical trials.

Amniotic membrane in the surgical management of acute toxic epidermal necrolysis

OBJECTIVE To report a new surgical technique to manage severe acute toxic epidermal necrolysis. DESIGN Two interventional case reports. PARTICIPANTS Two patients. Case 1: A 6-year-old boy had severe toxic epidermal necrolysis develop after being treated with trimethoprim and sulfamethoxazole for chronic otitis media. Both eyes and eyelids were affected. He underwent bilateral lysis of symblepharon and all adhesions and bilateral amniotic membrane transplantation to the entire ocular surface except the cornea. Loss of eyelid skin required transplantation of amniotic membrane to all four eyelids and strips of amniotic membrane at the eyelid margins. Case 2: An 8-year-old girl with severe toxic epidermal necrolysis associated with mycoplasma pneumonia had bilateral, diffuse keratoconjunctivitis, diffuse corneal epithelial defects, and bilateral symblepharon. Amniotic membrane transplantation was performed bilaterally, using a symblepharon ring in the left eye. INTERVENTION Amniotic membrane transplantation. MAIN OUTCOME MEASURES Preservation of normal ocular and eyelid surfaces and prevention of blindness. RESULTS Case 1: Thirty-six months after bilateral ocular surgery, there is no symblepharon, good ocular surface wetting, and an uncorrected bilateral vision of 20/20. Case 2: Amniotic membrane transplantation protected both ocular surfaces and prevented conjunctival contracture without adhesion of the eyelids to the ocular surface. The central vision was preserved. There was minimal peripheral corneal vascularization and mild conjunctival scarring of the tarsal conjunctival surface 34 months postoperatively. CONCLUSIONS These are the first cases of acute toxic epidermal necrolysis treated with amniotic membrane transplantation and the first use of the procedure on external eyelid surfaces with good healing of the eyelids. This new treatment for acute toxic epidermal necrolysis preserves normal ocular and eyelid surfaces and may prevent blindness.

Challenges and pitfalls in clinical trials of treatments for dry eye.

Clinical trials to evaluate the effectiveness of therapy for dry eye disease are challenging because of the nature of the disease, the multiple palliative methods used by patients to control their symptoms, and the potential limitations of the techniques available to evaluate therapeutic outcomes. This review identifies some of the pitfalls encountered in recent clinical trials in dry eye disease. The peculiarities of dry eye disease with respect to symptoms, signs, and patho- physiological changes are discussed. Potential problems that apply to all clinical trials, including patient selection, randomization in small populations, and assessment of the placebo effect, are presented with respect to dry eye clinical trials. Considerations regarding study design address inclusion/exclusion criteria and selection of outcome measures. Special attention is given to methods of symptom analysis, techniques of staining of the ocular surface, and grading systems for surface staining. Alternative methods to the standard clinical trial are mentioned to place them in perspective for overall evaluation of dry eye disease therapy. Finally, caveats are provided to encourage investigators to vigorously conduct future clinical trials in dry eye therapy.

Highly efficient ex vivo gene delivery into human corneal endothelial cells by recombinant adeno-associated virus.

Purpose: Gene delivery at high efficiency is crucial for cornea endothelial cell gene therapy. This study investigated the efficiency of gene transfer by recombinant adeno-associated virus (rAAV) in an organ culture system.Methods: Human cornea tissue was exposed to rAAV delivering green fluorescent protein (ss-rAAV2-CMV-GFP) for one hour and then cultured at 31ˆC for 2 weeks in a medium supplemented with growth factors. Endothelial cells expressing GFP gene were then identified.Results: High-efficiency gene transfer was found in over 90% of endothelial cells. Gene expression could be detected within 24 hours and remained stable up to 2 weeks in the organ culture system.Conclusions: The high-delivery efficiency and rapid induction of gene expression indicate that rAAV is a promising vector for cornea endothelial cell gene therapy for ocular diseases. Organ culture at 31ˆC using culture medium supplemented with growth factors significantly facilitates gene transfer into human corneal endothelium.

Cornea and external disease

New developments in cornea and external disease therapy are frequent and influence many aspects of the management of eye disease, including infectious disease, ocular surface disease, corneal surgery, and correction of refractive errors. Although media attention often highlights the novelty or potential impact of any advance, putting the new developments into proper perspective requires a more judicious and critical appraisal. The contributors to this issue of the Ophthalmology Clinics of North America provide that appraisal with respect to anti-infectious therapy, management of ocular surface disease, contact lens wear, novel surgical management of endothelial disease, and options for correction of refractive errors. The Charles T. Campbell Ophthalmic Microbiology Laboratory of the Eye and Ear Institute of the University of Pittsburgh provides a review of present-day ophthalmic microbiology. Regis Kowalski, MS, is the Technical Director of the Campbell Laboratory and reviews the experience of the laboratory with respect to antimicrobial sensitivity and emerging resistance; Francis Mah, MD, is the Associate Medical Director and reviews the scope of antibiotics and outlines new developments in antimicrobial options. A review of the present understanding of ocular surface disease summarizes dry eye therapy and management of meibomian gland disease. A summary of the new surgical approaches to treating ocular surface disease includes an overview of amniotic membrane transplantation by Thomas John, MD, and the options for limbal stem cell resurfacing by Drs. Kim and Holland. Perry Rosenthal, MD, describes the results of silicone scleral contact lens therapy for ocular surface disorders. New developments in contact lens therapy include the new generation of extended and continuous wear high-Dk materials, which are described by Peter Donshik, MD. An overview of the options for the use of therapeutic contact lenses completes an update of the evolving contact lens armamentarium. Finally, there is a presentation of novel innovations in surgical treatment of the cornea, which includes discussion and comparison of the flap (anterior) and limbal pocket (posterior) approaches to endothelial replacement. The issue concludes with a review of developments in LASIK and LASEK refractive surgery. To the authors who contributed to this issue, I extend my thanks and appreciation. To the reader, I express my hope that this review of the new developments in corneal and external disease treatment proves useful and provides perspective for optimal patient care.

The now and future therapy of the non-Sjögren's dry eye.

The National Eye Institute/Industry Workshop Classification for Dry Eye was developed to coordinate clinical research in dry eye, but also provides a framework to consider the various therapeutic options for managing dry eye disease.1 This classification differentiates between evaporative and tear-deficient dry eye, although it is important to recognize that both mechanisms for development of dry eye may occur in any given patient. Traditional therapy for the dry eye has concentrated on tear replacement with a variety of topical solutions. As our understanding of the structure and function of the tearfilm has improved, so has our knowledge of the important interactions this tearfilm has with the eyelid and the ocular surface.2 We are able to appreciate the variety of ocular conditions that can produce or aggravate dry eye, and with this appreciation we can develop a practical strategy for its management.3 This discussion proposes some therapeutic principles for the treatment of dry eye, and summarizes the things we presently do to treat dry eye, and then identifies new strategies that should soon be available for dry eye therapy. An important caveat before any treatment is employed, however, is that the patient must be fully educated as to the nature and characteristics of his/her dry eye disorder in order to assure understanding of the goals of therapy and to stimulate compliance with the recommended treatment.