sPLA2-IIa participates in ocular surface inflammation in humans with dry eye disease.

PURPOSE: To determine the roles of secretory phospholipase A2-IIa (sPLA2-IIa) in the inflammatory responses of the compromised ocular surface. METHODS: Conjunctival impression cytology (IC) samples and tears were collected from patients with mild to severe non-Sjogren's dry eye disease (DED) and normal controls. The IC samples were analyzed for transcription of sPLA2-IIa and inflammatory cytokine/chemokine genes using quantitative real-time RT-PCR (qRT2-PCR) and pathway-focus PCR-array. The tear samples were analyzed for 13 inflammatory cytokines and chemokines with Millipore 13-Plex kit. Finally, sPLA2-IIa-treated human conjunctival epithelial cell (HCjE) cultures were analyzed with a pathway-focused PCR array. RESULTS: Transcription of sPLA2-IIa was significantly increased in severe DED patients as compared to those of mild DED patients and normal controls. The transcription of inflammatory cytokines (IL-1ß, IL-4, IL-6, IL-17, TNF-α, IFN-γ), chemokines (IL-8, CXCL10, CXCL11, CXCL-14, CCR6, LTB) and matrix metalloproteinase 9 (MMP9) were simultaneously increased in the same IC samples of DED. Concentrations of IL-6 and IL-8 in tears were significantly higher in DED patients than those of the controls and positively correlated to DED severity scores. On the other hand, IL-2, IL-4, IL-10, IL-12 and IFN-γ were significantly lower in DED patients than those in the controls and inversely correlated to DEWS scores. Single treatment of sPLA2-IIa, IL-1ß or TNF-α of HCjE cells induced minimal to no PGE2 production. When sPLA2-IIa was added to HCjE cells that were pre-treated with pro-inflammatory cytokines (TNF-α or IL-1ß), significant stimulation of PGE2 production was observed, concurrent with the extensive transcriptional changes of many inflammatory cytokines/chemokines and their receptors. CONCLUSION: sPLA2-IIa activity was elevated and not only associated with inflammatory changes in DED patient samples, but was also found to cooperate with TNF- α and IL-1ß to induce inflammatory response in human conjunctival epithelial cells. Understanding the roles of sPLA2-IIa in ocular surface inflammation may lead to better strategies for the treatment of chronic inflammation associated with DED and other ocular inflammatory conditions.

Long-term follow-up of corneal graft survival following bone marrow transplantation in the Maroteaux-Lamy syndrome.

PURPOSE: To present a case of Maroteaux-Lamy syndrome (MLS, mucopolysaccharidosis [MPS] type VI) who underwent bone marrow transplantation (BMT) for gene transfer at the age of 13, and penetrating keratoplasty at the age of 17, and maintained clear corneal grafts bilaterally for 13 years. To our knowledge, this is the longest follow-up reported on corneal graft survival in a patient with MLS and BMT. METHODS: In 1982, BMT was successfully performed on a 13-year-old girl with MLS with growth retardation, typical facial features, skeletal and joint deformities, hepatosplenomegaly, cardiopulmonary dysfunction, and corneal clouding. Corneal transplantation was done on the left eye in 1986, and on the right eye in 1987 (6 months later) without difficulty or complication. RESULTS: Thirteen years postoperatively, the patient was systemically well, and both eyes retained clear corneal grafts. CONCLUSION: BMT retarded further dysfunction from MLS, and the corneal transplants retained clarity. Further controlled studies with longer follow-up are required to establish the efficacy of BMT in ocular manifestations of MPS or MLS.

Long-term follow-up of Intacs from a single center.

PURPOSE: To evaluate the long-term visual results in patients having Intacs placement for the correction of mild myopia. SETTING: Department of Ophthalmology, Mount Sinai School of Medicine and the Mount Sinai Hospital of Mount Sinai NYU Health, New York, New York, USA. METHODS: Patients with mild myopia (spherical equivalent between -0.75 and -4.50 diopters [D]) were enrolled to have Intacs placement between May 1995 and March 1999 under United States Food and Drug Administration Phase II and Phase III clinical trials for intrastromal corneal ring segments (ICRS). Six insert thicknesses were evaluated: 0.21, 0.25, 0.30, 0.35, 0.40, and 0.45 mm. The long-term results evaluated were uncorrected visual acuity (UCVA), maintenance of best spectacle-corrected visual acuity (BSCVA), predictability and stability of the refractive effect, induced manifest refraction cylinder, slitlamp findings, self-reported visual symptoms, and maintenance of mesopic contrast sensitivity. RESULTS: One hundred fourteen eyes of 73 patients were enrolled; 113 eyes of 72 patients received Intacs. There were no serious intraoperative or postoperative complications. The mean follow-up was 17.5 months +/- 8.9 (SD). At the end of this period (number of eyes evaluated = 100), the UCVA was 20/40 or better in 95 eyes (95.0%), 20/20 or better in 72 (72%), and 20/16 or better in 41 (41%). None of the 113 eyes lost 10 or more letters or 2 or more lines of preoperative BSCVA. The mean change in the cycloplegic refraction spherical equivalent for the 6 insert thicknesses was as follows: -0.75 +/- 0.00 D for 0.21 mm; -1.17 +/- 0.42 D for 0.25 mm; -2.00 +/- 0.54 D for 0.30 mm; -2.59 +/- 0.53 D for 0.35 mm; -3.09 +/- 0.54 D for 0.40 mm; and -3.82+/-0.80 D for 0.45 mm. The refractive correction was within +/-1.0 D of the predicted outcome in 103 eyes (92.0%) and within +/-0.5 D in 72 eyes (63.7%). Intacs were removed from 6 eyes (5.3%). All 4 eyes for which data were available 3 months after removal returned to within +/-0.5 D of their preoperative manifest refraction spherical equivalent. Intacs were exchanged because of undercorrection in 2 eyes (1.8%). These eyes gained 3 and 5 lines of UCVA 12 months and 18 months, respectively, after the exchange procedure. Overall, 85.7% (36/42) of the patients were satisfied with the results of the Intacs procedure. CONCLUSION: Intacs safely and effectively corrected mild myopia. Placement is a brief, easy outpatient procedure. The refractive effect was predictable and stable over long-term follow-up. Results from a limited number of removal and exchange procedures indicate that Intacs are removable and adjustable.

Two-year outcomes of intrastromal corneal ring segments for the correction of myopia.

OBJECTIVE: To evaluate the safety and efficacy of Intrastromal Corneal Ring Segments (ICRS) for the correction of myopia. DESIGN: Nonrandomized, comparative trial. PARTICIPANTS: Patients enrolled in the United States Food and Drug Administration phase II and phase III clinical trials of the ICRS had best spectacle-corrected visual acuity (BSCVA) of 20/20 or better, myopia of -1.00 to -3.50 diopters (D), and a cylindrical correction of 1.00 D or less as measured by manifest refraction. INTERVENTION: Surgical correction of myopia with an ICRS. MAIN OUTCOME MEASURES: Efficacy was assessed by predictability of refractive outcome (deviation from predicted cycloplegic refraction spherical equivalent), stability of refractive effect, and postoperative uncorrected visual acuity. Safety was assessed by adverse events, maintenance or loss of preoperative BSCVA, and induced manifest refraction cylinder. RESULTS: Four hundred fifty-two patients were enrolled at 11 investigational sites in both studies. Of the 454 surgical attempts, 449 received an ICRS in one eye (0.25, 0.30, and 0.35 mm in 148, 151, and 150 eyes, respectively). First surgeries were attempted in 452 patients. An ICRS was successfully implanted in 447 initial eyes, and 5 surgeries were discontinued. Of the five discontinued surgeries, three patients subsequently exited from the study, and two patients went on to have the ICRS implanted in the second eye, bringing the total number of successful implants to 449 patient eyes. Month 24 postoperative follow-up was completed on 358 patients (80%). At month 24, 328 of 354 eyes (93%) were within +/-1.00 D of predicted refractive outcome. Refraction changed by 1 D or less in 97% of eyes (421/435) between 3 and 6 months after implantation and in 99% (343/348) between months 18 and 24. Before surgery, 87% of eyes (390/448) saw worse than 20/40 uncorrected; 24 months after surgery, 55% of eyes (196/358) saw 20/16 or better, 76% (271/358) saw 20/20 or better, and 97% (346/358) saw 20/40 or better. Although two eyes (2/358; 0.5%) lost two or more lines of BSCVA at 24 months; visual acuity in both was 20/20 or better. Intraoperative complications included anterior corneal surface perforation (three eyes) and anterior chamber perforations (two eyes, one during an attempted exchange procedure); all healed spontaneously without suturing and without loss of BSCVA. The ICRS was repositioned in five eyes to increase correction. Postoperative complications in one eye each were infectious keratitis, shallow segment placement, and loss of two lines of BSCVA at two or more consecutive examinations (subsequently regained). CONCLUSIONS: The ICRS safely, predictably, and effectively reduced or eliminated myopia of -1.00 to -3.50 D. The refractive effect was stable over time.

Efficacy of polyclonal antibodies for treatment of ocular herpes simplex infection.

PURPOSE: Herpes simplex virus (HSV) can cause corneal infections in humans and lead to permanent scarring, loss of vision, and blindness. Current treatment of epithelial HSV keratitis consists of using antiviral DNA analogs. In this study, we used in vitro and in vivo models to evaluate the efficacy of six polyclonal antibodies to HSV recombinant surface glycoprotein D in treating ocular epithelial HSV. METHODS: Confluent cultures of African Green monkey kidney fibroblasts (Vero cells) and normal 3-to 5-lb female New Zealand White rabbits were infected with HSV type 1, strain RE. In vitro virucidal and antiviral assays were performed, and the best of the compounds was chosen for the in vivo stage. Animals were carefully monitored until day 5 after HSV-1 inoculation, then arbitrarily divided into groups receiving, for 14 days, varying doses of: polyclonal antibodies four times a day, polyclonal antibodies three times a day, trifluorothymidine (current treatment of choice and the positive control) nine times a day, or 0.9% physiologic saline nine times a day. The animals were followed up in a masked fashion and carefully monitored for severity and resolution of the HSV infection by biomicroscopy (slit lamp) examination and viral cultures using standardized plaque assays. RESULTS: All six of the compounds tested were effective in vitro, but one compound in particular, SP-510-50, was superior. It was used for the in vivo testing and showed antiviral efficacy in a dose-dependent manner, and at dosing four times a day, it was of comparable efficacy to trifluorothymidine (nine times a day). CONCLUSIONS: We conclude that polyclonal antibodies to glycoprotein D appear to be effective antiviral agents in vitro and in vivo in a rabbit model of HSV-1 keratitis and show promise as a new antiviral treatment for ophthalmic use.

Recurrent ocular herpes simplex keratitis following excimer laser photorefractive keratectomy in a rabbit model.

PURPOSE: Reactivation of latent herpes simplex virus (HSV) by excimer laser photorefractive keratectomy(PRK) has been reported previously in the literature. This study evaluates the extent of such HSV reactivation and determines whether corneal de-epithelialization prior to PRK or the laser treatment itself induces this response. METHODS: Twenty three normal 1.5-2.5 kg New Zealand white rabbits were infected on the surface of the cornea with HSV-1, strain RE. The animals were monitored until resolution and then divided into two treatment groups: 1) de-epithelialization alone, and 2) de-epithelialization plus laser. Animals were evaluated in a masked fashion by clinical examination and viral cultures twice a week through day 28. RESULTS: The reactivation rate for group 1 (de-epithelization alone) was 0.0%, and for group 2 (PRK) was 67% by slit lamp biomicroscopy. Viral culture positivity rate matched these findings. CONCLUSIONS: Excimer laser (193 nm) treatment can trigger viral shedding and reactivation of herpetic ocular disease in the latently infected rabbit. De-epithelialization alone is not sufficient to cause such viral reactivation or keratitis. Our findings suggest that patients with a history of herpetic keratitis undergoing PRK are at increased risk of HSV reactivation as a result of exposure to the excimer laser.

Intrastomal corneal ring segments: reversibility of refractive effect.

PURPOSE: To evaluate the reversibility of refractive effect following removal of the ICRS (intrastromal corneal ring segments; Intacs). METHODS: Data from 34 eyes from which ICRS were removed during United States FDA Phase II and III clinical trials were evaluated with regard to segment size, loss or change of best spectacle-corrected visual acuity (BSCVA), any change of uncorrected visual acuity (UCVA), manifest spherical equivalent refraction, manifest cylinder refraction, stability of manifest cylinder refraction, and subjective visual symptoms. RESULTS: Out of 725 initial or contralateral eyes placed with the ICRS during Phase II and III clinical trials, segments were removed from 34 eyes (4.7%). Other than one (1/725, 0.1%) safety related ICRS removal, 30/725 (4.1%) were due to visual symptoms. ICRS removal was accomplished under topical anesthesia without complications in all eyes. The mean length of time the segments remained in the cornea after initial surgery was 10.3 +/- 5.4 months. At 3 months after ICRS removal, 21 eyes had monitored data available and were within +/-1 line or 10 letters of their preoperative BSCVA. Twenty eyes (20/21, 95%) returned to within +/-1.00 D of their preoperative manifest spherical equivalent refraction. All eyes had a stable refraction at the 3-month examination after removal, and a manifest spherical equivalent refraction within +/-1.00 D of their 1-month examination after removal. Nineteen eyes (19/21, 90%) returned to within +/-2 lines and 16 eyes (16/21, 76%) returned to within +/-1 line of preoperative UCVA. CONCLUSION: The ICRS (Intacs) was easily and safely removed, and eyes returned to preoperative refractive status within 3 months.

Conductive keratoplasty for the correction of hyperopia.

BACKGROUND/PURPOSE: Conductive keratoplasty (CK) is a surgical technique that delivers radio frequency (350 kHz) current directly into the corneal stroma through a Keratoplasty tip inserted into the peripheral cornea at 8 to 32 treatment points. A full circle of CK spots produces a cinching effect that increases the curvature of the central cornea, thereby decreasing hyperopia. We report here the 12-month results of a 2-year, prospective, multicenter US clinical trial conducted to evaluate the efficacy, safety, and stability of CK. METHODS: A total of 233 patients (401 eyes) with preoperative hyperopia of +0.75 to +3.00 D and < or = 0.75 D of astigmatism (mean preoperative manifest refractive spherical equivalent = +1.76 D +/- 0.60) were enrolled into the study at 13 centers and underwent CK treatment. RESULTS: Twelve-month postoperative data are available on 203 eyes for safety and stability and 171 eyes for safety, stability, and efficacy. A total of 91% had uncorrected visual acuity (UCVA) of 20/40 or better, and 51% had UCVA of 20/20 or better. Manifest refractive spherical equivalent was within +/- 0.50 D in 58%, within +/- 1.00 D in 91%, and within +/- 2.00 D in 99%. The mean change in residual refraction was 0.26 D +/- 0.49 between 3 and 6 months, 0.09 D +/- 0.37 between 6 and 9 months, and 0.13 D +/- 0.39 between 9 and 12 months. CONCLUSIONS: One-year data show safety and efficacy of CK in the treatment of hyperopia. Changes in residual refractive error after CK appeared to be small, suggesting that a stable refraction could be achieved by 6 months.

Intraoperative PAR corneal topography system (CTS): comparison of its keratometric readings to manual keratometer, auto-keratometer, EyeSys Corneal Analysis system, and slit lamp PAR CTS in healthy eyes.

PURPOSE: To compare the keratometric readings obtained from Intraoperative PAR Corneal Topography System (IOPAR) to those produced by manual keratometer (Mnl-Km), autokeratometer (Auto-Km), EyeSys CAS (EyeSys Corneal Analysis System) and slit lamp PAR CTS in healthy eyes. METHODS: All instruments were calibrated prior to use and only data from the best image obtained was used for statistical analysis. Simulated keratometry readings obtained from the central 3-mm zone of the corneas by IOPAR, including flat (K1) and steep (K2) keratometry readings, average keratometric power (AK), astigmatism (As) (difference between steep and flat keratometry readings) and the axis of the steep meridian (Ax) were compared to those from four other units. The latter units were also compared among themselves. Statistical analysis was done for right and left eyes separately. For each variable, average differences between the measurements taken from pairs of instruments were estimated, with corresponding 95% confidence intervals. The degree of agreement between pairs of instruments on individual measurements was additionally assessed, via the use of "Bland-Altman"-type plots, and estimates of the proportion of cases achieving satisfactory agreement. Additionally, for every variable, the average of the measurements taken from the different instruments were compared. RESULTS: Forty-five (22 right and 23 left) normal corneas of 26 volunteers were examined. On the average, IOPAR tended to measure K1 higher than slit lamp PAR CTS system. Because K2 measurements taken by the IOPAR were higher than that of all other instruments, the As measurements, on the average, were also higher than that of others, with the exception of the PAR CTS. For the same reasons, the IOPAR produced average AK readings that were higher than those taken by EyeSys CAS and PAR CTS. When the individual measurements taken by the IOPAR were compared with each of the other units, according to the arbitrary designation of satisfactory agreement within +/-0.5 D (for K1, K2, AK, and As) and +/-20 degrees (for Ax), for almost all parameters, proportion of differences that were within the agreement range varied from 0.33 to 0.82, with wide confidence intervals (confidence interval lower limits ranging from 0.20 to 0.61 and upper limits ranging from 0.62 to 0.94). CONCLUSIONS: IOPAR is a clinically useful topographic system, producing qualitative and quantitative data in the operating environment that, in normal corneas, on the average, matches those produced by the other units in the clinic. When individually analyzed, its keratometric measurements may show greater variations with respect to other units. Further studies with multiple examiners, in corneas with high or irregular astigmatism are required to establish its reproducibility and efficacy.

Is intraoperative topography predictive of postoperative topographical changes following refractive surgery?

PURPOSE: To evaluate the usefulness of measuring corneal topography intraoperatively by Intraoperative PAR Corneal Topography System (IOPAR CTS) to predict the postoperative topographical changes in patients undergoing refractive surgery. METHODS: Topographical measurements of 9 eyes of 9 patients were taken by IOPAR CTS: 6 immediately after Intrastromal Corneal Ring Segments (ICRS) placement surgery and 3 immediately after Photorefractive Keratectomy (PRK) surgery. The topographical images taken by IOPAR CTS were analyzed to determine the quality of the image produced and the correlation of the keratometric data from the central 3 mm of cornea with measurements taken from an autokeratometer (Auto-Km) and the EyeSys Corneal Analysis System (CAS) for the same eyes taken three months following the procedure. RESULTS: At the 3-month postoperative exam, the correlation coefficients for flat (K1), steep (K2), and average keratometry (AK) readings produced by the Auto-Km and the EyeSys CAS were quite high. However, the correlation coefficients for K1, K2, AK, As or steep meridian axis (Ax) readings taken intraoperatively by IOPAR CTS were quite low when compared to the readings taken by either the Auto-Km or EyeSys CAS three months postoperatively. CONCLUSION: We found IOPAR CTS, relatively difficult to perform in the operating room during refractive surgical procedures and not useful clinically in predicting the postoperative topographical changes induced by ICRS or PRK procedure. Further studies are required to establish the efficacy and reproducibility of the instrument.

Characteristics of the myopic patient population applying for refractive surgery.

PURPOSE: Assessment of the characteristics of the myopic patient population applying for refractive surgery in order to determine the potential market for myopic refractive surgery. METHODS: Records of consecutive patients who responded to an advertisement for refractive surgery to correct myopia were evaluated retrospectively with regards to patient demographics and the amount and distribution of the refractive error. Data were compared to that available from population-based statistics for distribution of myopia in the general population. For statistical analysis, one sample Student's t-test and two tailed Student's t-test were utilized. RESULTS: Two hundred fifty seven patients (140 women and 117 men) responded to an advertisement for refractive surgery during the six month period between January and June 1998. Mean spherical equivalent (SEQ) of the patient population was -4.59+/-2.54 D (min;-0.25 D, max;-15.75 D) right eye (OD) and -4.62+/-2.82 D (min;-0.25 D, max;-15.25 D) left eye (OS). Among the patients who had myopia with an astigmatism of at most 1.00 D (n=165), the distribution of refractive error was statistically significantly different from that obtained from population-based statistics, such that, although most of the myopic population (40%) had an SEQ of -1.00 to -2.25 D, the majority of our patients (54.8%) who applied for myopic refractive surgery had an SEQ of -2.50 to -5.00 D. Another striking difference was that, although patients with an SEQ more than -6.00 D were a minority(2%) in the population study, in our study group, they comprised 16.7% of the patients seeking refractive correction. The difference between the SEQ of the right and left eyes ranged from 0.00 D to 13.0 D (mean, 0.89+/-1.5 D), 47.1 % having a difference of at most +/-0.5 D between the two eyes. The mean cylindrical error in the patient population was 0.69+/-0.93 D (min: 0, max: -4.5) OD and 0.69+/-0.96 D (min: 0, max: -4.5) OS. There were no statistically significant differences between the distribution of SEQ or cylindrical refractive error between males and females. CONCLUSION: Although a population-based study reported that most of the myopic population (40%) had an SEQ of -1.00 to -2.25 D, the majority of our patients (54.8%) who applied for myopic refractive surgery had an SEQ of -2.50 to -5.00 D. On the other hand, while patients with an SEQ of -6.00 D and more constituted only about 2% of the general population, they accounted for 16.7% of our study population. Therefore, the refractive characteristics of the patient population applying for myopic refractive surgery may not necessarily parallel that of general population-based statistics. In order to establish a more effective refractive surgery practice, it is feasible to perform local studies and reevaluate the requirements of your practice accordingly.

Valacyclovir for the prevention of recurrent herpes simplex virus eye disease after excimer laser photokeratectomy.

PURPOSE: A variety of factors have been reported as inducing the reactivation of latent herpes simplex virus (HSV), among them stress, trauma, and UV radiation. Excimer laser photorefractive keratectomy (PRK) is a surgical procedure utilizing a 193 nm ultraviolet light to alter the curvature of the cornea and hence correct vision. Reactivation of ocular herpes simplex keratitis following such excimer laser PRK has been reported. All published cases of HSV reactivation following excimer laser treatment in humans are reviewed. The present study evaluates whether stress, trauma of the corneal de-epithelialization prior to the laser, or the excimer laser treatment itself to the stromal bed induces this ocular reactivation of the latent HSV, and whether a systemic antiviral agent, valacyclovir, would prevent such laser PRK-induced reactivation of the HSV. METHODS: Forty-three normal 1.5- to 2.5-kg New Zealand white rabbits were infected on the surface of the cornea with HSV-1, strain RE. The animals were monitored until resolution, and then all animals were divided into 5 treatment groups: (1) de-epithelialization only, intraperitoneal (i.p.) saline for 14 days; (2) de-epithelialization plus laser, i.p. saline for 14 days; (3) de-epithelialization plus laser, valacyclovir 50 mg/kg per day i.p. for 14 days; (4) de-epithelialization plus laser, valacyclovir 100 mg/kg per day i.p. for 14 days; (5) de-epithelialization plus laser, valacyclovir 150 mg/kg per day i.p. for 14 days. Animals were evaluated in a masked fashion by clinical examination biweekly and viral cultures biweekly through day 28. RESULTS: The reactivation rates were as follows: group 1, 0%; group 2, 67%; group 3, 50%; group 4, 17%; and group 5, 0%. Viral titers were negative in animals that had no reactivation but persistently positive in those that had reactivation (day 6 through day 28). CONCLUSIONS: Excimer laser (193 nm) treatment can trigger reactivation of ocular herpes disease (67%) and viral shedding in the latently infected rabbit. De-epithelialization alone is not sufficient to cause reactivation or viral shedding. Prophylaxis with intraperitoneal valacyclovir decreases the recurrence rate in a dose-response fashion. At 150 mg/kg per day, there are no recurrences. The presence of persistent viral shedding in reactivated animals may correlate with cases of late HSV recurrence reported in humans undergoing excimer treatment. The data suggest that humans undergoing excimer laser procedures for correction of refractive errors or treatment of corneal scars with a history of herpetic keratitis are at increased risk for reactivation. Such patients, however, may appropriately be considered for prophylactic systemic antiviral medication at the time of the laser procedure in order to decrease the possibility of recurrence.

Photorefractive keratectomy after intrastromal corneal ring segment explantation.

PURPOSE: To describe a case of photorefractive keratectomy after removal of intrastromal corneal ring segments from the cornea. METHODS: During United States Food and Drug Administration Phase III Trials for intrastromal corneal ring segments (ICRS), the implanted segments were removed from the cornea of the right eye of a patient because of dissatisfaction with glare, halos, and fluctuating vision. Ten months after ICRS explantation, the-patient underwent a photorefractive keratectomy procedure to the same eye. RESULTS: One month after removal of the ICRS, the patient's manifest refraction was within +/- 0.50 diopters of his original manifest refraction. Photorefractive keratectomy was planned to the same eye 6 months later. At the first attempt, the epithelium could not be removed with the laser and scrape technique, and residual epithelium was noted at the vertical meridian (12 o'clock) corneal incision site, which had been used for ICRS surgery and explant; therefore, the procedure was aborted. At the second attempt, with a mechanical epithelial brush (AMOILS Epithelial Scrubber; Innova, Inc, Toronto, Canada), the epithelium was removed with ease. After this, photorefractive keratectomy was done without difficulty or complication. At his most recent 8-month postphotorefractive keratectomy examination, the patient had an uncorrected visual acuity of RE: 20/16, with a manifest refraction of -0.75 to 0.75 x 170 degrees, a faint haze at the site of the stromal channel, and a small scar at the incision site on slit-lamp examination. CONCLUSIONS: Intrastromal corneal ring segments can be readily removed from the cornea, if required. In this case, the refraction returned to its preoperative state soon after the explant procedure and remained stable over time. Photorefractive keratectomy was performed as a secondary refractive surgical procedure after the removal of ICRS without difficulty or complication. However, removal of the epithelium is probably best accomplished with the use of an epithelial brush, considering the changes in the epithelial adherence in a postsurgical cornea. Further studies are required to establish the safety and efficacy of secondary refractive surgical procedures after ICRS explantation.

Adjustability of refractive effect for corneal ring segments.

PURPOSE: To evaluate the safety and efficacy of adjustability of the refractive effect of intrastromal corneal ring segments (ICRS, Intacs). METHODS: Data from four patients who had their initial Intacs removed and exchanged for new Intacs of different thickness sizes during a United States Food and Drug Adminstration Phase II clinical trial were evaluated with regard to segment size, reasons for exchange, duration within the cornea before exchange procedure, loss or change of spectacle-corrected visual acuity, change of uncorrected visual acuity, manifest refraction, cycloplegic refraction, topography after exchange, and stability of refraction. RESULTS: The exchange procedure was performed in two patients due to undercorrection and in two for overcorrection. The length of time the segments remained in the cornea after initial surgery varied from 6 to 15 months (mean, 10.25 +/- 4.03 mo). The most recent examination occurred between 4 to 18 months (mean, 10.0 +/- 6.32 mo) following the exchange procedure and showed improved uncorrected visual acuity with a range from 20/16 to 20/20 and a gain of 2 to 7 lines of uncorrected visual acuity compared to baseline. No eyes lost any lines of spectacle-corrected visual acuity following the exchange procedure and all preserved their preoperative spectacle-corrected visual acuity of 20/16. The intended refractive correction was achieved in the first few days of the exchange procedure and remained stable. CONCLUSION: In these four eyes that were over- or undercorrected after initial Intacs placement, segment thickness sizes were exchanged after 6, 8, 12, and 15 months without complication and with final uncorrected visual acuities of 20/16 to 20/20.

Topographic predicted corneal acuity with intrastromal corneal ring segments.

PURPOSE: To evaluate predicted optical quality of the central anterior corneal surface before and after the intrastromal corneal ring segment (ICRS) refractive procedure using a clinical videokeratoscope and software index developed for that purpose. METHODS: Predicted corneal acuity, a topographically derived index provided with the EyeSys System 2000 videokeratscope, representing potential optical quality of the cornea, was assessed preoperatively and at postoperative month 3 in 94 eyes that received an ICRS to treat -1.00 to -6.00 D of myopia. Predicted corneal acuity was calculated by determining the difference between a measured cornea and its best-fit ellipses for reflected ring circumferences within the central 3 mm diameter zone. RESULTS: Preoperative predicted corneal acuity was 20/10 in 92 of 94 eyes (98%). At month 3 after the ICRS procedure, 48 (51%) of moderately myopic eyes were corrected to 20/20 or better, 96% (90 eyes) were corrected to 20/40 or better, and 98% of eyes (92 eyes) had a predicted corneal acuity of 20/10. For the eyes with a predicted corneal acuity of 20/10, spectacle-corrected visual acuity was normally distributed between 20/10 and 20/25. CONCLUSION: Predicted corneal acuity did not change significantly from baseline in eyes with an ICRS. This suggests that topographic irregularities in the central 3 mm of the cornea detectable by predicted corneal acuity software were not induced in the central cornea with the ICRS.

Efficacy of cobalt chelates in the rabbit eye model for epithelial herpetic keratitis.

PURPOSE: A new class of antiviral agent, cobalt chelates (the CTC series), was evaluated for treating epithelial herpetic keratitis, consequent stromal disease being the major infectious cause of blindness in industrial nations. METHODS: Effects of CTC complexes were monitored in cell cultures and in a rabbit eye model, either infected with herpes simplex virus type 1 (HSV-1) or uninfected. Several antiviral concentrations of CTC complexes nontoxic to Vero cells were administered to rabbit eyes with HSV-1-induced keratitis. Corneal surface virus titers were measured, and corneal lesions of epithelial keratitis were monitored by slit-lamp microscopy and scored. Recovery rates and incidence were compared in eyes treated with CTC complexes, placebo, or clinically formulated trifluorothymidine (Viroptic), using nonparametric statistics. RESULTS: All CTC complexes inhibited HSV-1 replication in vitro, CTC-96 being best. CTC-96, CTC-23, and CTC-67 eliminated (<1 plaque-forming unit[pfu]) corneal surface HSV-1 (otherwise >10(5) pfu) in order of descending potency, but CTC-82 was ineffective. CTC-96 (either 5 microg/ml six times daily or 10 microg/ml five times daily) accelerated herpetic dendritic keratitis recovery better than or the same as trifluorothymidine (10 mg/ml nine times daily). CTC complexes were nontoxic to Vero cells continuously exposed to < or =25 microg/ml; 50 microg/ml of CTC 96 nine times daily did not irritate uninfected rabbit eyes. CONCLUSION: Topical CTC-96 applications were at least as effective as Viroptic in diminishing disease signs and corneal surface virus at concentrations less than one-thousandth that of Viroptic.

Botulinum toxin increases tearing in patients with Sjögren's syndrome: a preliminary report.

Three patients with Sjögren's syndrome (SS) who had severe xerophthalmia and blepharospasm received botulinum toxin injections for the treatment of their blepharospasm. They had a remarkable increase in tearing, measured by Schirmer's test, and a decrease in signs and symptoms of dry eyes after botulinum toxin injection periorbitally for blepharospasm. The mechanism for this increased tearing is unclear, but suggests a potential treatment for patients with severe xerophthalmia with SS.

The intrastromal corneal ring segments. Phase II results for the correction of myopia.

OBJECTIVE: The purpose of the study was to evaluate the safety and efficacy of the intrastromal corneal ring segments (ICRS) for the correction of myopia. DESIGN: A 2-year phase II clinical trial of ICRS was initiated in May 1995. The investigational plan specifies that 150 patients with sighted eyes, requiring myopic corrections from -1.00 to -6.00 diopters (D), will each receive ICRS in 1 eye. The patient population will be divided into approximately five patients per ICRS thickness (0.25, 0.30, 0.35, 0.40, and 0.45 mm) per site. Six investigational sites are participating in the trial. PARTICIPANTS: Fifty-nine men and 43 women requiring myopic corrections were enrolled at four U.S. investigational sites. These 102 patients each received the ICRS product in 1 eye. INTERVENTION: Correction of myopia. MAIN OUTCOME MEASURES: Efficacy of ICRS was assessed with respect to the trial endpoints of predictability of refractive effect, uncorrected visual acuity (UCVA), stability of UCVA, maintenance of best spectacle-corrected visual acuity and stability of refractive effect. RESULTS: As shown by the available month-3 data (99 patients; all device thicknesses), 95 (96%) of 99 patients had a UCVA of 20/40 or better. Ninety-eight (99%) of 99 patients were within 2 lines of their preoperative best spectacle-corrected visual acuity. The average change (with standard error) in cycloplegic refraction (spherical equivalent) achieved by ICRS thickness was -1.27 +/- 0.09 D (0.25 mm), -2.13 +/- 0.16 D (0.30 mm), -2.56 +/- 0.15 D (0.35 mm), -3.77 +/- 0.37 D (0.40 mm) and -4.16 +/- 0.24 D (0.45 mm). Seventy-seven percent (76/99) of the patients were within +/-1.00 D of their intended correction. When the ICRS was removed in two cases, both patients returned to within 0.75 D of their preoperative manifest refraction. CONCLUSIONS: The ICRS appears to be a viable and effective alternative for the treatment of myopia. Additionally, as indicated by the explant data, the ICRS's refractive effect may be reversible upon removal of the device.

Risk factors for herpes simplex virus epithelial keratitis recurring during treatment of stromal keratitis or iridocyclitis. Herpetic Eye Disease Study Group.

AIMS: Possible risk factors were evaluated for herpes simplex virus (HSV) epithelial keratitis in patients with stromal keratouveitis. METHODS: The study population included 260 patients who had active stromal keratitis and/or iridocyclitis without epithelial disease and who were enrolled in one of three clinical trials of the Herpetic Eye Disease Study. Study treatment involved a 10 week course of topical placebo, topical prednisolone phosphate, or topical prednisolone phosphate with oral acyclovir. All groups received topical trifluridine four times daily for 3 weeks then twice daily for another 7 weeks. Patients were examined for HSV epithelial keratitis for 16 weeks. RESULTS: Dendritic or geographic epithelial keratitis occurred in 12 (4.6%) study patients. Adverse effects attributable to trifluridine prophylaxis were acute allergic blepharoconjunctivitis in 10 (3.8%) study patients and corneal epithelial erosions in 11 (4.2%) study patients. No significant difference in the occurrence of HSV epithelial keratitis was found among the study treatment groups: one (2.0%) of 49 topical placebo treated patients, nine (6.5%) of 138 patients treated with topical corticosteroids without acyclovir, and two (2.7%) of 73 patients treated with topical corticosteroids and oral acyclovir. Univariate exponential models suggested that patients with a history of previous HSV epithelial keratitis and non-white patients were more likely to develop HSV epithelial keratitis during treatment of stromal keratouveitis. CONCLUSION: Individuals with prior HSV epithelial keratitis and certain ethnic groups may have a higher rate of recurrent epithelial keratitis during the acute treatment of HSV stromal keratouveitis.