Trans-stromal epithelial cyst after multiple lamellar keratoplasties - Case report and review of literature.

DESIGN: Single Observational Case Report. SETTING: A 67-year-old male of Persian descent had a complex systemic and ocular history prior to a right penetrating keratoplasty (PK) reported here. The clinical diagnoses leading to the PK included Cogan's syndrome, chronic uveitis, secondary glaucoma, and corneal stromal scarring, presumed secondary to a corneal ulcer diagnosed on the second visit to our clinic. The specimen described here had been in place for 11 months and 17 days after the third failed Descemet stripping endothelial keratoplasty (DSEK). Visual acuities had ranged from 20/100 to 20/400 in both eyes. Visual acuity in the right eye just before surgery was 20/400. Intraocular pressures were 22 mmHg in both eyes with functioning Ahmed glaucoma shunts. The stromal cyst was not suspected preoperatively and no clinical imaging was performed. STUDY METHODS: Histopathology including serial sections and immunohistochemistry. RESULTS: Histologic study demonstrated a trans-stromal corneal epithelial cyst without goblet cells that extended through a 500 µm gap in the donor tissue surface and edge. CONCLUSIONS: This large stromal cyst was an unusual complication of serial posterior lamellar keratoplasties and we postulate that multiple prior posterior lamellar grafts may have been a risk factor for this complication. Anterior segment imaging with either anterior segment optical coherence tomography or high-resolution ultrasound would likely have detected this stromal cyst.

Aqueous shunts for glaucoma.

BACKGROUND: Aqueous shunts are employed for intraocular pressure (IOP) control in primary and secondary glaucomas that fail medical, laser, and other surgical therapies. OBJECTIVES: This review compares aqueous shunts for IOP control and safety. SEARCH STRATEGY: We searched CENTRAL, MEDLINE, PubMed, EMBASE, NRR all in January 2006, LILACS to February 2004 and reference lists of included trials. SELECTION CRITERIA: We included all randomized and quasi-randomized trials in which one arm of the study involved shunts. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data for included studies and a third adjudicated discrepancies. We contacted investigators for missing information. We used fixed-effect models and summarized continuous outcomes using mean differences. MAIN RESULTS: We included fifteen trials with a total of 1153 participants with mixed diagnoses. Five studies reported details sufficient to verify the method of randomization but only two had adequate allocation concealment. Data collection and follow-up times were variable.Meta-analysis of two trials comparing Ahmed implant with trabeculectomy found trabeculectomy resulted in lower mean IOPs 11 to 13 months later (mean difference 3.81 mm Hg, 95% CI 1.94 to 5.69 mm Hg). Meta-analysis of two trials comparing double-plate Molteno implant with the Schocket shunt was not done due to substantial heterogeneity. One study comparing ridged with standard double-plate Molteno implants found no clinically significant differences in outcome. Two trials investigating the effectiveness of adjunctive mitomycin (MMC) with the Molteno and Ahmed implants found no evidence of benefit with MMC. Two trials that investigated surgical technique variations with the Ahmed found no benefit with partial tube ligation or excision of Tenon's capsule. One study concluded there were outcome advantages with a double versus a single-plate Molteno implant and one trial comparing the 350 mm(2) and 500 mm(2) Baerveldt shunts found no clinically significant advantage of the larger device but neither of these trials included all patients randomized. One study suggested improved clinical outcome when MMC was employed with a newly described shunt including ultrasound supporting the conclusion. One small study did not demonstrate an outcome advantage to systemic steroid use postoperatively with single-plate Molteno shunts. One study comparing endocyclophotocoagulation (ECP) with Ahmed implant in complicated glaucomas found no evidence of better IOP control with Ahmed implant over ECP. AUTHORS' CONCLUSIONS: Relatively few randomized trials have been published on aqueous shunts and methodology and data quality among them is poor. To date there is no evidence of superiority of one shunt over another.

Changes in axial length following trabeculectomy and glaucoma drainage device surgery.

AIM: This study examines the changes in axial length (AL) after trabeculectomy and glaucoma drainage device (GDD) surgery and enabled an equation to be derived allowing prediction of AL change after filtering surgery. METHODS: This was a prospective, interventional case series from the Glaucoma Service of the Doheny Eye Institute. PATIENT POPULATION: One eye of 39 patients undergoing trabeculectomy and 22 undergoing Baerveldt tube shunt implantation for uncontrolled glaucoma. INTERVENTION: These patients had AL measurements by non-contact, partial coherence interferometry preoperatively, at 1 week, 1 month, and >3 months after surgery. MAIN OUTCOME MEASURES: Axial length and intraocular pressure were compared at preoperative and postoperative visits. Postoperative intraocular pressure (IOP) was categorised as hypotonous (0-4 mm Hg), low (5-9), normal (10-17), and high (18 or more). RESULTS: There was a statistically significant reduction in IOP after 3 months of -12.8 (SD 1.5) mm Hg following trabeculectomy (p<0.001), and -10.7 (1.9) mm Hg after GDD (p<0.001). There was a statistically significant reduction in AL, which was similar after trabeculectomy and GDD at all time points (p<0.001), of -0.15 (0.03) and -0.21 (0.04) mm (1 week), -0.18 (0.02) and -0.10 (0.02) mm (1 month), and -0.16 (0.03) and -0.15 (0.03) mm (3 months). At 3 months or later the AL reduction was related to postoperative IOP and to the amount of IOP reduction (p<0.05, stepwise multiple regression). 10.2% (4/39) of trabeculectomy patients had hypotony after 3 months, with a mean AL reduction (-0.39 (0.11)) that was statistically significantly lower (p<0.01) than the other trabeculectomy eyes (-0.14 (0.15)). CONCLUSIONS: There is a small but statistically significant decrease in AL after both trabeculectomy and GDD surgery, greater in eyes that are hypotonous after surgery. The authors suggest that AL reduction can be predicted after 3 months by the formula: AL reduction (mm) = -199+0.006 x IOP reduction+0.008 x final IOP.

Comparing the fixed combination dorzolamide-timolol (Cosopt) to concomitant administration of 2% dorzolamide (Trusopt) and 0.5% timolol -- a randomized controlled trial and a replacement study.

PURPOSE: To compare the intraocular pressure (IOP) lowering effect of concomitant administration of 0.5% timolol and 2% dorzolamide and a fixed combination dorzolamide-timolol (Cosopt) To critically evaluate discrepancies between phase 3 clinical trials and prior replacement studies. DESIGN: A prospective, randomized, controlled clinical trial and a prospective, non-randomized comparative replacement trial. PARTICIPANTS/INTERVENTIONS: In a national multicentre trial, 131 patients were randomized to dorzolamide-timolol or a topical carbonic anhydrase inhibitor (CAI) and non-selective beta-blocker following a 1-month run-in using the separate components. Peak (maximal drug effect) and trough (minimal drug effect) IOPs were measured at baseline and 1 month after treatment. The replacement therapy study enrolled 404 consecutive glaucoma patients using a non-selective beta-blocker and dorzolamide and changed treatment to the fixed combination. Mean IOPs at the same time of day were compared before and 1 month after changeover. MAIN OUTCOME MEASURE: The main outcome measure was IOP, comparing baseline and on-therapy measurements at study conclusion between the two arms of the randomized trial and before and after switching therapy in the replacement trial. RESULTS: In the randomized trial, the mean baseline peak and trough IOPs were 18.4 and 21.0 mmHg in the group randomized to combination therapy and 17.6 and 19.8 mmHg in the dual drug group. After randomization and treatment for four weeks, the peak and trough IOPs were 17.6 and 19.5 mmHg in the combination group and 17.3 and 19.0 mmHg in the concomitant group. The percentage change in IOP was -3.2% at peak and -6.5% at trough for the combination and -0.3 and -3.2% for the concomitant group. These differences did not show statistical significance. In the replacement study, mean baseline IOP was 19.4 mmHg. Four weeks after initiation of treatment on the fixed combination, a significant additional IOP reduction of 1.7 mmHg (-8.8%) was observed (P < 0.0001). Overall, 81% of eyes exhibited equal or lower IOP on the fixed combination compared with concomitant therapy. CONCLUSION: The results of the randomized trial indicate that the fixed combination dorzolamide-timolol (Cosopt) was as effective as its components in controlling IOP, confirming results seen in phase 3 clinical trials. However, in the replacement study, utilization of the combination drug offered a statistically significant additional IOP reduction (P < 0.0001), which duplicates results from previous replacement studies.

Performance of a new, low-volume, high-surface area aqueous shunt in normal rabbit eyes.

PURPOSE: This experimental study was conducted to report perfusion characteristics of small diameter, cylindrical aqueous shunts in normal rabbit eyes and to test the hypothesis that decreasing bleb diameter would decrease capsular fibrosis, as evidenced by a thinner capsule forming around the implant. These two properties increase hydraulic conductivity of the fibrous membrane forming around the device, resulting in a more effective filtering shunt. METHODS: Cylindrical latex tubes with the distal portion of the sidewall removed were implanted under the conjunctiva. The proximal, intact end of tubing was inserted into the anterior chamber and ligated to prevent hypotony. The ligature was released after 1 week to inflate the bleb. Animals were again anesthetized at 6 or 12 weeks after ligature release and in vivo perfusion experiments conducted using a miniperfusion system and a water manometer. Perfusion of the implant with latex microspheres was performed before the animals were killed. Capsule diameters were measured in situ using calipers under a dissecting microscope after excision of orbital tissues and before fixation for histologic study. Membrane hydraulic conductivity (outflow per unit membrane area at unitary pressure gradient, microL/min/mm2/mmHg) was calculated using data obtained during perfusion experiments and compared with results of other studies. Capsule thickness was measured histologically. RESULTS: Cylindrical filtration membranes with thin (15-20 microm) capsules formed around latex implants. Bleb diameters consistently measured 1 mm at all points along their length before formaldehyde fixation. Hydraulic conductivity was measured and found to be eight times higher than that reported for capsules around conventional implants. Decreased diameter (16:1 for Baerveldt and 13:1 for Molteno implants) produced a proportional decrease in surface tension on the wall. This resulted in decreased capsule thickness, from 222 microm for Baerveldt implants in rabbit eyes and from 150 microm for Molteno implants in monkey eyes to less than 20 microm for the shunting device studied here. CONCLUSION: As a consequence of Laplace's law, reduction in bleb diameter reduces surface tension on the bleb, reducing capsular fibrosis and consequently capsule thickness, thus increasing hydraulic conductivity. Increased hydraulic conductivity increases the effectiveness of the filtering surface. Cylindrical geometry allows reduced bleb volume yet maintains total surface area that is proportional to the length of the implant, which is unlimited and customizable for each eye by simply cutting the length of implant needed.

Randomized clinical trial of the 350-mm2 versus the 500-mm2 Baerveldt implant: longer term results: is bigger better?

OBJECTIVE: To report the longer term results of a randomized, clinical trial comparing the 350-mm2 and the 500-mm2 Baerveldt glaucoma implants. DESIGN: Extended follow-up on a randomized, controlled trial. PARTICIPANTS: Between March 1991 and April 1993, 107 patients with uncontrolled intraocular pressure (IOP) due to non-neovascular glaucoma associated with aphakia, pseudophakia, or failed filters were randomly assigned for surgical placement of either the 350-mm or the 500-mm2 Baerveldt implant at the Doheny Eye Institute. METHODS: A random-numbers table was used to assign each patient to one of the two groups. Preoperative IOPs and visual acuities were recorded. Clinical records were reviewed to ascertain postoperative IOPs, visual acuities, number of medications used, and implant-related complications that occurred throughout the follow-up period. MAIN OUTCOME MEASURES: Success was defined as IOP of 6 mmHg or greater and of 21 mmHg or less in two or more consecutive follow-up visits without further glaucoma surgery or loss of light perception attributable to glaucoma. RESULTS: The overall success rates were 87% for the 350-mm2 group and 70% for the 500-mm2 group (P = 0.05). Average follow-up was 37 months (range, 1-76 months) for the 350-mm2 group and 34 months (range, 5-77 months) for the 500-mm2 group. The life-table success rates declined over time for both implant groups, from a high of 98% for the 350-mm2 group and 92% for the 500-mm2 group at 1 year to a cumulative success rate of 79% for the 350-mm2 group and 66% for the 500-mm2 group at 5 years. Visual acuities were better or remained the same in 50% of the patients in the 350-mm2 group and 46% of those in the 500-mm2 group. Complications during the 5-year follow-up were also statistically similar. CONCLUSIONS: The longer term results show that the 350-mm2 Baerveldt implant is more successful than the 500-mm2 implant for overall IOP control. Interval comparisons indicate a higher rate of success for the 350-mm2 implant in the first, second, third, fourth, and fifth years of implantation. Visual acuities, implant-related complications, and average IOPs were statistically indistinguishable between the two groups.

Latanoprost treatment for glaucoma: effects of treating for 1 year and of switching from timolol. United States Latanoprost Study Group.

PURPOSE: To determine the efficacy and safety of latanoprost treatment for 1 year in glaucoma patients, and to evaluate the effects of switching from timolol to latanoprost therapy. METHODS: Latanoprost 0.005% was topically applied once daily without masking for 6 months in 223 patients with elevated intraocular pressure after previous treatment with latanoprost once daily or 0.5% timolol twice daily for 6 months in a multicenter, randomized, double-masked, parallel group study. RESULTS: Compared with baseline values before treatment, a significant (P < .0001) diurnal reduction in intraocular pressure of 6 to 8 mm Hg was maintained with minimal fluctuation for the duration of treatment. When treatment was switched from timolol to latanoprost, intraocular pressure was reduced by 1.5 +/- 0.3 mm Hg (mean +/- SEM; 8% change in intraocular pressure; 31% of the intraocular pressure reduction produced by timolol; P < .001) compared with the change in intraocular pressure in patients remaining on latanoprost therapy. Of the patients initially enrolled, 95% successfully completed treatment. There was a slight overall increase in conjunctival hyperemia in patients who switched from timolol to latanoprost, but no change in those who continued latanoprost. The timolol-induced reduction of resting heart rate returned to baseline levels after switching to latanoprost. Of the 247 patients treated with latanoprost during the masked and/or open-label studies, 12 (5%) demonstrated a definite (n = 4) or possible (n = 8) increase in iris pigmentation. CONCLUSIONS: Latanoprost is a well-tolerated ocular hypotensive agent that appears to be more effective than timolol in reducing intraocular pressure. The increase in iris pigmentation appears to be harmless but requires further investigation.

Trabeculectomy with intraoperative 5-fluorouracil.

BACKGROUND AND OBJECTIVE: To investigate the outcome and complication rates of trabeculectomy following the combined use of intraoperative, topical 5-fluorouracil (5-FU) and low-dose, postoperative subconjunctival 5-FU injections. PATIENTS AND METHODS: Forty-one eyes of 41 patients with advanced, medically uncontrolled glaucoma underwent trabeculectomy with intraoperative episcleral application of 5-FU (50 mg/ml for 5 minutes). A variable number of subconjunctival 5-FU injections were administered postoperatively at the discretion of the operating surgeon. RESULTS: Six-, 12-, and 15-month life-table success rates (5 mm Hg < or = intraocular pressure [IOP < or = 21 mm Hg) were 100%, 97%, and 83%, respectively. Mean postoperative IOP was 12.1 +/- 4.3 mm Hg. An average of 2.2 +/- 1.6 (range 0 to 7) supplemental subconjunctival 5-FU injections were administered postoperatively. Corneal epithelial erosions developed in 7 (17%) of the eyes. Five of 7 patients who underwent subsequent surgical procedures maintained successful control of IOP at an average of 11.0 +/- 4.8 (range 5 to 16) months after the secondary surgery. CONCLUSION: Trabeculectomy with intraoperative 5-FU is effective in controlling IOP while possibly minimizing the need for frequent postoperative injections and the occurrence of corneal epitheliopathy.

Glaucoma associated with uveitis.

Raised intraocular pressure is a common and frequently serious complication of anterior uveitis. The milieu of inflammatory cells, the mediators they release, and the corticosteroid therapy used to treat the uveitis can participate in the pathogenesis of uveitic glaucoma. These factors alter the normal anatomic structure of the anterior chamber and angle, influencing aqueous production and outflow. These changes act to disrupt the homeostatic mechanisms of intraocular pressure control. Structural changes in the angle can be acute, such as in secondary angle closure with pupillary block glaucoma, or chronic, such as combined steroid-induced and secondary open angle glaucoma. Management of uveitic glaucoma may be difficult because of the numerous mechanisms involved in its pathogenesis. Diagnostic and therapeutic decisions are guided by careful delineation of the pathophysiology of each individual case. The goal of treatment is to minimize permanent structural alteration of aqueous outflow and to prevent damage to the optic nerve head. This article reviews the pathogenesis of uveitic glaucoma, with specific attention to etiology. Medical and surgical therapies are also discussed, with emphasis on the more recent developments in each category.

Annular peripheral choroidal detachment simulating aqueous misdirection after glaucoma surgery.

PURPOSE: The purpose of the study was to define a newly recognized complication after glaucoma surgery and to recommend a therapeutic regimen. METHODS: Eighteen patients diagnosed initially as having aqueous misdirection after glaucoma surgery, but who subsequently were found by ultrasonography to have an annular peripheral choroidal detachment that resulted in secondary angle closure glaucoma, were studied. Ten of these patients were treated with topical cycloplegics and corticosteroids, and 8 were treated with drainage of suprachoroidal fluid. Outcomes of these two treatment methods were compared. RESULTS: Annular peripheral choroidal detachment reliably was diagnosed with ultrasonography. Of the variables studied, time elapsed before resolution of the annular peripheral choroidal detachment was noted to be statistically significant (P < 0.00005). Immediate resolution followed drainage of suprachoroidal fluid, whereas a mean of 19.6 days was required for resolution after medical therapy. CONCLUSIONS: Annular peripheral choroidal detachment should be considered in the differential diagnosis of a flat or shallow anterior chamber with normal or high intraocular pressure after glaucoma surgery. The diagnosis of annular peripheral choroidal detachment can be confirmed most reliably by ultrasonography. Medical therapy is as effective as is surgery, although a significantly longer time to resolution is required.

Interobserver and intraobserver variability in the detection of glaucomatous progression of the optic disc.

PURPOSE: To evaluate the potential value of obtaining follow-up stereoscopic photographs on glaucoma suspects in identifying progressive optic nerve damage. METHODS: Nineteen sets of stereoscopic optic disc photographs, reflecting one eye from each of 19 patients at two time points, were selected from the records of subjects enrolled in the Glaucoma Screening Study. By consensus, three experts judged 13 of these eyes to have progressive glaucomatous optic nerve damage. Four other ophthalmologists who were masked to the expert panel evaluation then assessed glaucomatous progression in the same eyes. They were asked to evaluate glaucomatous progression in three ways: first, by drawing the optic nerve head appearance from initial stereoscopic photographs and later comparing their own drawings to follow-up stereoscopic photographs; second, by comparing serial stereoscopic photographs directly; and third, by comparing drawings of the optic nerve head made by another examiner to the follow-up photographs. RESULTS: Neither sensitivity nor specificity was consistently better for serial stereoscopic photographs than for drawings. Individual ophthalmologist agreement rates with the expert panel's determinations of progression were 23-62% when examiners compared their own drawings to follow-up photographs, 54-71% when examiners compared serial stereoscopic photographs, and 38-85% when comparing another ophthalmologist's drawings to follow-up photographs. CONCLUSION: Baseline stereoscopic photographs of the optic nerve head did not substantially improve recognition of progressive glaucomatous optic nerve damage when compared with the use of baseline drawings of the optic nerve head made from photographs in subjects who developed visual loss in the interim.

Long-term histologic studies of the Baerveldt implant in a rabbit model.

PURPOSE: The Baerveldt glaucoma implant is an aqueous shunting device with large surface area that is installed through a single-quadrant conjunctival incision. A rabbit model of the Baerveldt implant was created to obtain serial histology and clinical information over 1 year. METHODS: Modified versions of the Baerveldt implant (110 or 160 mm2) were implanted in 18 normal New Zealand white rabbit eyes. The rabbits were examined periodically and their intraocular pressures (IOPs) recorded. They were killed at monthly intervals to obtain histology of the bleb capsules. RESULTS: Thin capsules were present at 1 month, which consisted of lamellar collagen deposition surrounded by a granulomatous reaction with multinucleate giant cells. Inflammatory cells (probably macrophages) were scattered on the inner bleb surface. The granulomatous reaction resolved after 4 months. Subsequently, capsule thickness and cellularity remained relatively stable, although the collagen stroma became less compact over time. Sixteen rabbit eyes had initial IOP reductions of > or = 3 mm Hg compared with fellow eyes, which persisted up to 4 weeks postoperatively. Seven eyes (39%) exhibited a hypertensive phase (IOP exceeded that of fellow eye by > or = 3 mm Hg) from 2 weeks to 3 months postoperatively. CONCLUSION: The Baerveldt explant is surrounded by a fibrous capsule that matures over time. The bleb histology in the rabbit model is similar to that described with the Molteno implant in primates and humans, except for the eventual development of a fibroblastic inner lining in the rabbit model. This contrasts with primate and human models, in which the inner lining remains an open mesh.