Claes H. Dohlman

Keratoprosthesis: preoperative prognostic categories.

Purpose. Recent advances aimed at preventing and treating complications after keratoprosthesis surgery have improved prognosis, but it has been suspected that various preoperative diagnoses may carry substantially different postoperative outcomes. This article attempts to clarify the ranking of prognostic categories for patients undergoing keratoprosthesis surgery. Methods. A retrospective review of the outcome in a recent series of 63 patient eyes operated at the Massachusetts Eye and Ear Infirmary between 1990 and 1997 and followed up for a minimum of 21 months. Anatomic retention of the device and the loss of vision caused by complications were recorded. The patients were divided into four categories according to preoperative cause. Results. Anatomically, one keratoprosthesis extruded spontaneously. Another 10 were permanently removed because of complications. Of the 63 eyes, 10 never achieved a visual acuity of at least 20/200 vision because of preexisting retinal or optic nerve damage. The remaining 53 had a visual acuity of 20/200 to 20/20 as follows: Stevens–Johnson syndrome (n = 7), after 2 years: 33%, after 5 years: 0%; chemical burn (n = 17), after 2 years: 64%, after 5 years: 25%; ocular cicatricial pemphigoid (n = 20), after 2 years: 72%, after 5 years: 43%; graft failure in noncicatrizing conditions (dystrophies, degenerations, or bacterial or viral infections) when a repeat graft was expected to have a poor prognosis (n = 19), after 2 years: 83%, after 5 years: 68%. The difference in outcome between the Stevens–Johnson syndrome outcome group and the graft failure group or the ocular cicatricial pemphigoid group was statistically significant. In the group of 53 eyes, visual acuity was restored to 20/200 to 20/20 for a cumulative total of 138 years. Conclusion. Outcome of the keratoprosthesis surgery varied markedly with preoperative diagnosis. Most favorable was graft failures in noncicatrizing conditions, whereas Stevens–Johnson syndrome was the worst. Ocular cicatricial pemphigoid and chemical burns occupied a middle ground. The difference between the groups seemed to correlate with the degree of past preoperative inflammation.

Penetration routes of topically applied eye medications

Tritium-labeled hydrocortisone acetate and pilcarpine hydrochloride solutions were topically applied to the eyes of rabbits. In one group of animals, the drugs were excluded from contact with the cornea by a cylindrical well glued to the eye surface. In another group, the drug solutions were allowed contact with the entire anterior surface of the eye. Total application time in all cases was five minutes, then the eyes were flushed with saline. Samples of aqueous humor, stroma, and iris-ciliary body were taken after five, 20, 35, 65, and 125 minutes and counted in a liquid scintillation counter. With hydrocortisone, up to 70 times more drug reached the stroma when the cornea was exposed; 40 times more reached the iris. Peak stromal levels occurred by 20 minutes, dropping to one third of peak value by two hours. With pilocarpine, about five times more drug reached the iris-ciliary body when corneal access was allowed; the level peaked in about five minutes. These results illustrate the important role of tear film distribution and blinking in delivering remotely applied drugs over the cornea with subsequent entry to interior sites.

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.

The Boston Keratoprosthesis in Stevens-Johnson Syndrome

PURPOSE To evaluate the use of the Boston keratoprosthesis (KPro) in patients with Stevens-Johnson syndrome (SJS). DESIGN Retrospective, noncomparative, interventional case series. METHODS Sixteen eyes of 15 patients with SJS underwent KPro surgery at the Massachusetts Eye and Ear Infirmary from January 2000 through December 2005. The preoperative, operative, and postoperative findings were recorded. All patients underwent either the type I or type II Boston KPro surgery by one surgeon (C.H.D.). Retention of the prosthesis, best-corrected visual acuity, the need for surgical revision, and postoperative complications were recorded. The outcomes were compared with those of an earlier group of patients from the 1990s. RESULTS The mean age of patients was 50+/-18 years (range, 23 to 74 years), and the mean duration of their disease was 10+/-6.6 years. The mean follow-up period was 3.6+/-1.5 years (range, 10.2 months to 5.6 years). Ten eyes underwent type II KPro surgery, whereas six eyes underwent type I KPro surgery. Twelve eyes (75%) achieved a visual acuity of 20/200 or better after surgery, with eight eyes (50%) achieving excellent vision of 20/40 or better. Visual acuity was maintained at 20/200 or better over a mean period of 2.5+/-2.0 years. Preexisting glaucoma was found to be a significant risk factor for visual loss. There were no cases of KPro extrusion or endophthalmitis. CONCLUSIONS KPro in SJS has improved, largely because of the introduction of vancomycin prophylaxis and better glaucoma treatment. It seems to be superior to standard penetrating keratoplasty, with or without allografted stem cell transplantation, as judged from the literature. However, the outcome of the KPro in SJS is still substantially less favorable than in nonautoimmune diseases.

A new method for the determination of the swelling pressure of the corneal stroma in vitro

A new method for the determination of the swelling pressure of the corneal stroma and sclera has been developed. A tissue button at any degree of hydration is placed between two glass filters. The upper filter is movable and connected to a capacitance transducer; the lower filter is fixed. When 0·9% NaCl is brought in contact with the tissue, slight swelling occurs and the force is recorded. The swelling is restricted considerably by the transducer. Therefore, a steady force is rapidly reached, usually within 30 min. Experiments were carried out on steer, rabbit and human corneal stroma and on steer sclera over a wide range of hydrations. The swelling pressure of the normal corneal stroma was found to be about 60 mm Hg and that of the normal sclera about 17 mm Hg. The swelling pressure of the sclera showed a greater dependence on hydration than did that of the corneal stroma.

Advances in Boston keratoprosthesis: enhancing retention and prevention of infection and inflammation.

Advances in standard corneal transplantation since the beginning of the 20th century has restored vision to many patients with corneal blindness. Among this group of patients, there is a subgroup, such as repeat graft failures and cicatrizing diseases in whom a standard corneal transplant carries a poor prognosis. Thus, according to a recent large study, grafts for all causes remained clear in 70% of the cases after 5 years. In a separate study, only 20% of the first regrafts similarly survived, whereas all repeat regrafts failed in the same 5-year period. The outcome studies have shown similar results. Hence, the need for keratoprosthesis (KPro) as an alternative to a standard corneal transplant. The concept of using artificial material in place of a human donor cornea is not new; Pellier de Quengsy in 1789 first suggested this concept at the time of the French Revolution. For subsequent history, see Albert and Jakobiec’s Principle and Practice of Ophthalmology, 3rd ed. Approximately, a dozen centers worldwide are presently involved in the development of KPro using different materials, innovative designs and surgical techniques. Widespread use of the KPro is limited due to difficult surgical techniques of some KPro varieties, time involvement on part of the surgeon and patient, and past reputation of high rate of complications (Table 1). Most importantly there is a lack of awareness among the corneal community of the availability, efficacy, and

Successful Prevention of Bacterial Endophthalmitis in Eyes with the Boston Keratoprosthesis

Purpose: To determine the influence of topical vancomycin prophylaxis on the incidence of bacterial endophthalmitis in eyes with a Boston Keratoprosthesis (KPro). Methods: A retrospective chart review was performed for 255 eyes of 231 patients who received a KPro between March 1990 and December 2006. Preoperative diagnoses were burn, ocular cicatricial pemphigoid (OCP), Stevens-Johnson Syndrome (SJS), and graft failure/other. Patients used topical antibiotic prophylaxis for the duration of the KPro: polymyxin-trimethoprim or a quinolone in the 1990s, or a quinolone with or without vancomycin beginning in late 1999. For each KPro eye, the follow-up interval was divided into months on or off vancomycin (vancomycin versus no-vancomycin group). The incidence of endophthalmitis was calculated with Kaplan-Meier survival curves. Results: The 255 eyes were followed for 673.6 patient-years (mean, 2.64 years; range, 1 week to 13 years). There were 18 cases of bacterial endophthalmitis; 17 occurred at least 6 weeks postoperatively (range, 1.5 to 46 months). Gram-positive cocci caused over 80% of cases. Only 1 case, due to an atypical mycobacterium, occurred in a patient using vancomycin. The incidence of bacterial endophthalmitis was lower in the vancomycin group than in the no-vancomycin group: 0.35% versus 4.13% per patient-year (P = 0.001). It was also lower in SJS eyes using vancomycin versus no vancomycin: 1.76% versus 18.39% per patient-year (P = 0.009). In eyes with preoperative diagnoses of burn, OCP, or graft failure/other, the incidence in the vancomycin group was zero. Conclusion: Topical vancomycin plus a quinolone is effective in preventing bacterial endophthalmitis in KPro eyes.

Importance of nutrition to corneal grafts when used as a carrier of the Boston Keratoprosthesis.

Purpose: Necrosis, melt, and perforation have historically been frequent around a Keratoprosthesis (KPro), even resulting in extrusion or endophthalmitis. Autoimmune diseases such as Stevens-Johnson Syndrome (SJS) and Ocular Cicatricial Pemphigoid (OCP) have been notorious in this respect. The purpose of this study was to compare the frequency of tissue melt after implantation of two designs of the Boston KPro, one allowing much better access of nutrition from the aqueous humor to the carrier graft. Methods: We retrospectively reviewed charts of 157 eyes implanted since 1990 with a poly (methylmethacrylate) Boston KPro, including 79 eyes implanted with the model having 8 small (1.3-mm diameter) holes in the back plate, and 78 eyes implanted with the older solid back plate. We compared the frequency of tissue melts between the two KPro designs, for all implants as well as for subgroups based on preoperative diagnosis. Results: In total, 48/157 eyes (31%) developed some degree of tissue melt around the stem, including 8/79 eyes (10%) in the back plate with holes group and 40/78 eyes (51%) in the solid back plate group (P < 0.0001). Among the melts in the back plate with holes group, 4/8 (50%) suffered from an underlying autoimmune disease such as SJS or OCP. Conclusions: The Boston KPro design with a back plate containing holes protects the overlying corneal tissue from necrosis and melts. This improved situation is likely due to increased aqueous access and better nutrition to the corneal graft cells. In addition, this study confirms earlier work regarding the particular corneal fragility of patients with autoimmune diseases.

Keratoprosthesis: an update.

Porous polytetrafluoroethylene and polyurethane skirt materials, as well as copolymers of poly (2-hydroxyethyl methacrylate), have shown promise in approaching the goal of a “biointegratable” keratoprosthesis. A novel fixation method that uses scleral haptics also has been introduced to increase stability. An all silicone device that can be sewn into position has been used successfully, temporarily, during vitreoretinal procedures. The prognosis of keratoprosthesis (KPro) procedures depends on the preoperative diagnosis: graft failure-noncicatrizing disease>ocular cicatricial pemphigoid>chemical burns>Stevens-Johnson syndrome. The likelihood of endophthalmitis after KPro surgery follows this scheme. Causative organisms tend to be gram-positive. Modified vitreoretinal techniques also have been developed, allowing successful treatment of posterior segment complications. The science of keratoprosthesis is advancing more rapidly than in previous years. However, use of KPro to address complicated corneal blindness worldwide remains limited. The authors conducted an English language literature review from January 1, 2000 to April 1, 2001 and describe advances of note in the field of keratoprosthesis design, materials, and medical and surgical management.

Repeat penetrating keratoplasty versus the Boston keratoprosthesis in graft failure.

Modern penetrating keratoplasty is a procedure that successfully restores vision in thousands of patients a year. Approximately 33,000 procedures are performed per annum in the United States, the majority of these successful because of what is commonly referred to as the immune privilege of the cornea. Although we have only recently begun to elucidate the specific unique and complex immune responses involved in keratoplasty rejection, clinical experience in the low-risk keratoplasty category—keratoconus being the prototypical example—is that first-time allografts generally have an excellent prognosis often with only minimal topical steroid use (greater than 95% clear grafts at 4 and 10 years). This compares favorably with solid organ allograft survival rates such as in renal transplantation, in which systemic immunosuppression with cyclosporin is necessary. Although it is possible for grafts to remain clear for decades (Fig. 1), graft failure for all diagnostic categories (assuming a single graft per eye) is not insignificant. The Australian corneal graft registry found overall corneal failure to be 25% at 3 years and 30% at 5 years; Ing et al found the rate to be 21% at 10 years, Patel et al 26% at 15 years, Price et al 9% at 5 years, and Bishop et al 35% at 5 years. Outcome appears to vary widely with geographic region, and although the primary etiology for graft failure appears to shift with time, graft failure is thought to continue by steady attrition beyond past 10 years. Although most episodes of rejection occur in the first or second year after penetrating keratoplasty, late endothelial failure without clinical evidence of a significant episode of rejection is the most significant cause of failure in grafts that last past 5 years, although the actual rate of cell loss decreases with time.