IOP-lowering and drug-sparing effects of trabectome surgery with or without cyclodialysis ab interno.

PURPOSE: To compare the postoperative intraocular pressure (IOP) after ab interno trabeculectomy (AIT; trabectome surgery) alone or combined with cyclodialysis ab interno (AITC). PATIENTS AND METHODS: Forty-three eyes with insufficiently controlled open-angle glaucoma were included in this consecutive case series. All eyes received AIT, combined with phacoemulsification and IOL-implantation in phakic instances, with or without additional cyclodialysis ab interno. Postoperative visual acuity, IOP, number of IOP-lowering medications and complications were registered over 12 months. RESULTS: A total of 19 eyes (14 patients) received AIT and 24 (19 patients) received AITC. Both groups were comparable for baseline IOP (AIT: 19.7 ± 8.2 mmHg; AITC: 19.4 ± 6.8 mmHg; p = 0.96), there was a comparable IOP reduction after 6 months (AIT: - 3.8 ± 12.3, median (interquartile range (IQR)): - 3.8 (- 7.8-4.8) mmHg; AITC: - 4.9 ± 8.3, median (IQR): - 2.0 (- 10.8-2.0) mmHg; p = 0.95) and 12 months (AIT: - 4.3 ± 6.6, median (IQR): - 4.0 (- 8.0 to - 1.0) mmHg; AITC: - 3.7 ± 6.7, median (IQR): - 1.5 (- 5.5 to - 0.5) mmHg; p = 0.49). While final visual acuity was similar between the groups, they differed regarding topical IOP-lowering medications (baseline: AIT 2.9 ± 1.2 and AITC 2.9 ± 1.2; 1 year after surgery: AIT 2.6 ± 1.5 (p = 0.16) and AITC 1.3 ± 1.3; p < 0.001)). Depending on the definition, a complete or qualified success of 33.4-45.8% was achieved in AITC compared to 15.8-21.1% in AIT. CONCLUSION: The additional suprachoroidal outflow when AIT is combined with cyclodialysis ab interno (AITC) seems to result in an additional drug sparing effect for at least 1 year without critical safety signals. Thus, AITC might be further investigated prospectively prior to advocating its use in routine minimally invasive glaucoma surgery.

Effect of Preoperative Intraocular Pressure in Patients with and without Intolerance to Their IOP-Lowering Medication on the Outcome of Trabectome Surgery.

PURPOSE: This study aimed to compare the effect of trabectome surgery in patients with and without intolerance to their medication and with preoperatively sufficiently controlled, insufficiently controlled, and uncontrolled intraocular pressure (IOP) on the surgical outcome. PATIENTS AND METHODS: A total of 155 eyes (133 patients) with different forms of open angle glaucoma with or without intolerance to their glaucoma medication undergoing trabectome surgery alone (AIT) or combined with phacoemulsification (phaco-AIT) were included in this retrospective monocentric study. Patients were corresponding to IOP ≤ 18 mmHg (controlled but glaucoma progression or intolerance, group 1), 19-26 mmHg (insufficiently controlled, group 2), and ≥ 26 mmHg (not controlled, group 3), respectively. Pre- and postoperative IOP and the number of IOP-lowering medications were registered over 12 months. Surgical success was defined as a postoperative IOP of ≤18mmHg and/or reduction of the topical treatment demand after 1 year. RESULTS: Of the 155 included eyes, 79 received AIT and 76 received phaco-AIT. Sixty-nine eyes had a preoperatively sufficiently controlled IOP, 63 had an insufficiently controlled IOP, and 23 had an uncontrolled IOP. In all groups, the IOP significantly dropped by 6 and 12 months after surgery (p < 0.001). Surgical success war similar in all groups [47.8% (group 1), 38.1 (group 2) and 34.8% (group 3); p= 0.47]. The effect of AIT on IOP and glaucoma medication independent of intolerance to the anti-glaucoma medication and type of surgery (AIT/phaco-AIT). CONCLUSION: Independently of the preoperative IOP, a satisfying surgical success was achieved using AIT. In instances that do not qualify for filtrating surgery, trabectome surgery alone or in combination with phacoemulsification thus represents a safe and effective minimally invasive glaucoma surgery technique regardless of an intolerance to the topical medication.

Pathophysiology of proliferative vitreoretinopathy in retinal detachment.

Because proliferative vitreoretinopathy cannot be effectively treated, its prevention is indispensable for the success of surgery for retinal detachment. The elaboration of preventive and therapeutic strategies depends upon the identification of patients who are genetically predisposed to develop the disease, as well as upon an understanding of the biological process involved and the role of local factors, such as the status of the uveovascular barrier. Detachment of the retina or vitreous activates glia to release cytokines and ATP, which not only protect the neuroretina but also promote inflammation, retinal ischemia, cell proliferation, and tissue remodeling. The vitreal microenvironment favors cellular de-differentiation and proliferation of cells with nonspecific nutritional requirements. This may render a pharmacological inhibition of their growth difficult without causing damage to the pharmacologically vulnerable neuroretina. Moreover, reattachment of the retina relies upon the local induction of a controlled wound-healing response involving macrophages and proliferating glia. Hence, the functional outcome of proliferative vitreoretinopathy will be determined by the equilibrium established between protective and destructive repair mechanisms, which will be influenced by the location and the degree of damage to the photoreceptor cells that is induced by peri-retinal gliosis.

Functional and anatomical outcomes of vitreoretinal surgery for posterior segment complications after elective cataract surgery.

PURPOSE: To assess the outcomes in patients who required 1 or more vitreoretinal interventions for posterior segment complications arising from elective uneventful cataract surgery. SETTING: Tertiary referral center, single-center study. METHODS: A retrospective interventional case series included 56 consecutive patients who were referred for surgical correction of posterior segment complications within 6 months of cataract surgery. The study period was between 1996 and 2003, and the minimum follow-up was 5 months. RESULTS: Posterior segment complications were resolved with a single surgical intervention in 40 cases (71.4%). Within 5 months of primary surgical correction, persisting or newly arising posterior segment complications were noted in 16 cases (28.6%). After a mean of 2.1 +/- 1.4 (SD) additional surgeries, the number of eyes with posterior segment problems decreased to 7 (12.5%) (P = .035). Posterior segment complications requiring more than 1 vitreoretinal intervention included retinal detachment, endophthalmitis, and choroidal hemorrhages. After primary correction surgery, the mean best corrected visual acuity increased from 0.15 +/- 0.24 to 0.37 +/- 0.33 (P = .001) after a single intervention and to 0.39 +/- 0.32 (P>.05) after additional interventions. Although the intraocular pressure (IOP) decreased from 21.8 +/- 16.6 mm Hg to 14.9 +/- 3.4 mm Hg (P = .008), 4 (7.1%) consecutive vascular optic atrophies occurred. A reduction in corneal transparency was observed in 46.4% of patients before primary surgical correction and 12.5% after primary surgical correction (P<.001). CONCLUSIONS: In many cases, posterior segment complications arising from cataract surgery could be repaired with favorable functional and anatomical outcomes by a single vitreoretinal intervention. Additional surgery, if requested, provided stabilization of the anatomical and functional outcomes.

Visual function in human ocular toxoplasmosis.

AIM: To assess functional impairment in terms of visual acuity reduction and visual field defects in inactive ocular toxoplasmosis. METHODS: 61 patients with known ocular toxoplasmosis in a quiescent state were included in this prospective, cross-sectional study. A complete ophthalmic examination, retinal photodocumentation and standard automated perimetry (Octopus perimeter, program G2) were performed. Visual acuity was classified on the basis of the World Health Organization definition of visual impairment and blindness: normal (> or =20/25), mild (20/25 to 20/60), moderate (20/60 to 20/400) and severe (<20/400). Visual field damage was correspondingly graded as mild (mean defect <4 dB), moderate (mean defect 4-12 dB) or severe (mean defect >12 dB). RESULTS: 8 (13%) patients presented with bilateral ocular toxoplasmosis. Thus, a total of 69 eyes was evaluated. Visual field damage was encountered in 65 (94%) eyes, whereas only 28 (41%) eyes had reduced visual acuity, showing perimetric findings to be more sensitive in detecting chorioretinal damage (p<0.001). Correlation with the clinical localisation of chorioretinal scars was better for visual field (in 70% of the instances) than for visual acuity (33%). Moderate to severe functional impairment was registered in 65.2% for visual field, and in 27.5% for visual acuity. CONCLUSION: In its quiescent stage, ocular toxoplasmosis was associated with permanent visual field defects in >94% of the eyes studied. Hence, standard automated perimetry may better reflect the functional damage encountered by ocular toxoplasmosis than visual acuity.

An ex-vivo, whole-globe porcine model of corneoepithelial wound healing tested using immunomodulatory drugs.

BACKGROUND: An efficient epithelial wound healing is essential for the preservation of vision. Hence, the effects of novel topical drugs on the ocular surface must be ascertained before clinical use. We have tested the utility of an ex vivo, whole-globe porcine screening model to serve as a partial substitute for resource- and time-consuming animal experiments. METHODS: Standardized corneoepithelial lesions, 5.0 mm in diameter and 40 microm in depth, were created with an Excimer laser in freshly enucleated porcine eyes. These were then exposed to control solutions (physiological saline (baseline), tissue-culture medium (positive control) and NH4 + (toxicity control)) and to three test agents (cyclosporin A, dexamethasone, and mitomycin C). The wound-healing response and toxic effects were monitored after 20-26 h by comparing lesion sizes. RESULTS: According to baseline data obtained using physiological saline, tissue-culture medium improved wound healing. The highest doses of NH4 + (1 M) and mitomycin C (1.0 mg/mL) elicited toxic effects (confidence interval according to Scheffé's post hoc test: -0.65 to -0.07 and -0.99 to -0.60, respectively). Under the same test conditions, cyclosporin A (0.1 to 10 mg/mL) and dexamethasone (0.1 to 10 mg/mL) had no influence on corneoepithelial wound healing. CONCLUSIONS: Drug screening with this ex vivo porcine model permits a reproducibly quantitative and time- and dose-dependent assessment of corneoepithelial wound healing. This model corresponds more closely to the clinical situation than cell culturing and may, therefore, be useful in evaluating novel pharmaceutical agents, thereby helping to cut down on the number of animal experiments performed prior to the instigation of clinical trials.

Specific antibody levels in the aqueous humor and serum of two distinct populations of patients with ocular toxoplasmosis.

The population of Erechim, Southern Brazil, is characterized by a high incidence of ocular toxoplasmosis, which is presumed to be of acquired origin. We wished to compare the local specific humoral immune response of individuals from this region with that of Swiss patients suffering from the same disease. Paired samples of aqueous humor and serum were withdrawn from 27 Brazilian and 50 Swiss patients presenting consecutively with active ocular toxoplasmosis. The total and specific levels of IgG in each of these were determined. The populations did not differ with respect either to age or sex. The serum levels of total IgG in Brazilian (10.8 g/l) and Swiss patients (11.1 g/l) were similar (p = 0.499), but the aqueous humor ones were higher in the former group (95 vs. 20 mg/l; p = 0.0001). The systemic and local levels of specific IgG were likewise higher in Brazilian patients [206 i.u. vs. 72 i.u. (p = 0.001) and 14 i.u. vs. 4 i.u. (p = 0.005), respectively] and the number of individuals without detectable levels of local specific IgG was correspondingly lower (11% vs. 54%; p = 0.0005). The Goldmann-Witmer coefficient (an index of local specific antibody production) did not differ between Brazilian and Swiss patients (2.1 vs. 0.08, respectively; p = 0.107). Our findings are indicative of a more pronounced uveovascular barrier breakdown in Brazilians than in Swiss patients with active ocular toxoplasmosis. That the systemic and local specific immune response is weaker in Swiss than in Brazilian patients has not been hitherto documented. This finding may reflect differences in the immunological handling of the infection.

Cryopreservation of human donor corneas with dextran.

PURPOSE: To assess freeze-thaw-induced endothelial cell loss by using phase-contrast microscopy and early morphologic changes within each layer of human donor corneas by using confocal microscopy. METHODS: Twenty-eight human corneas were cryopreserved in minimum essential medium containing 10% dextran with a molecular weight (MW) of 500,000 as an extracellular cryoprotectant, at a cooling rate of 1 degrees C/min and stored in liquid nitrogen at -196 degrees C. After thawing, the tissue was organ cultured to detect latent cell damage. In 22 of the corneas, the endothelial layer was subjected to routine phase-contrast microscopy after 24 hours of organ culturing. The other six specimens were evaluated layer by layer in a scanning slit confocal microscope after 6, 24, and 48 hours of organ culturing. RESULTS: Before cryopreservation, the mean +/- SD numerical density of endothelial cells was 1940 +/- 220 cells/mm(2). After cryopreservation and subsequent organ culturing, the endothelial cell density decreased to 1300 +/- 360 cells/mm(2), and two of the corneas had a completely necrotic endothelium (P = 0.001). Confocal microscopy revealed all corneal layers in each of the six specimens examined to be structurally integral after 48 hours of organ culturing. Although the reflectivity of some of the keratocytes was enhanced, there were no signs of keratolysis. CONCLUSIONS: The present study demonstrates that each corneal layer is capable of regaining its structural integrity after cryopreservation in the presence of dextran. Because the freeze-thaw-induced endothelial cell loss is still highly variable, the technique must be further refined before it can be applied clinically.

HSV-1 antigens and DNA in the corneal explant buttons of patients with non-herpetic or clinically atypical herpetic stromal keratitis.

BACKGROUND: Little is known about the role of HSV-1 in keratitis not primarily attributed to herpetic origin. This study therefore aimed to prospectively evaluate the corneal explant buttons of patients with non-herpetic or clinically atypical herpetic stromal keratitis (experimental group: non-HSK) for the presence of HSV-1 antigens and DNA, and to compare the findings with those from individuals with typical herpetic stromal keratitis (positive control group: HSK) or non-inflammatory degenerative keratopathy (negative control group). METHODS: Corneal buttons derived from 51 patients with HSK, from 72 with non-HSK and from 30 with degenerative keratopathy were prospectively collected and subjected to immunohistochemical analysis for HSV-1 antigens and to HSV-1 DNA amplification. RESULTS: In corneal buttons derived from patients with non-HSK, viral antigens were detected immunohistochemically in 8/72 cases and DNA amplified in 16/72. Corresponding values for the HSK group were 16/51 and 11/51. Taking viral antigen and DNA findings together, HSV-1 was detected in 18/72 (25%) patients with non-HSK and in 19/51 (37%) with HSK (p=0.2), but in only 2/30 (6%) individuals with non-inflammatory degenerative keratopathy. CONCLUSION: Since the detection frequencies for HSV-1 antigens and DNA were comparable in the HSK and non-HSK groups, Herpes may play an underestimated and as yet undefined role in non-herpetic and clinically atypical herpetic stromal keratitis, either as a primary trigger of the disease or as a secondary contributor to it. In this category of individuals, early anti-herpetic therapy should be considered if patients do not respond in the expected manner to treatment for non-herpetic stromal keratitis.

Analysis of risk factors for the outcome of primary retinal reattachment surgery in phakic and pseudophakic eyes.

BACKGROUND: To compare the preoperative risk profiles of phakic and pseudophakic eyes with primary retinal detachment and to assess their impact on the outcome of primary reattachment surgery. PATIENTS AND METHODS: 220 consecutive patients with primary retinal detachment, 165 phakic and 55 pseudophakic eyes were operated with scleral buckling alone or additional vitrectomy and followed up for 6 months. Pre-, intra- and postoperative risk factors were recorded and their impact on anatomical outcome after primary surgery in phakic and pseudophakic eyes was then compared in a multivariate regression analysis. RESULTS: The cumulative probability of anatomical success 6 months after surgery was similar in phakic (88.5 %) and pseudophakic eyes (86.3 %; log rank = 0.340). The most important risk factor for a different surgical outcome between phakic and pseudophakic eyes was the size of retinal detachment (p = 0.035). In phakic eyes the size of retinal detachment had no significant impact on surgical outcome (1 vs. 4 quadrants; log rank = 0.135); whereas in pseudophakic eyes a significant impairment on surgical outcome was found (1 vs. 4 quadrants; log rank < 0.001). The relative risk for failure of primary surgery due to retinal detachment of at least 3 quadrants was in phakic eyes 1.22 (CI: 0.71 - 1.70), in pseudophakic ones 1.81 (CI: 0.88 - 2.59). CONCLUSIONS: The outcome of primary retinal reattachment surgery in phakic and pseudophakic eyes is similar for retinal detachments up to 3 quadrants. In retinal detachments of more than 9 clock times, the size of retinal detachment impairs the surgical outcome in pseudophakic eyes more than in phakic ones. The combination of extraocular surgery with vitrectomy in pseudophakic eyes with retinal detachment of more than 9 clock times contributes to a better outcome.

[The pathogenesis of herpetic keratitis]. / Zur Pathogenese der herpetischen Keratitis.

BACKGROUND: Viral infections of Herpes origin are the most commonly encountered ones in man. The most important member of this family is the Herpes simplex virus (HSV), two varieties of which are known to exist: HSV-1 affects predominantly the upper half of the body, whereas HSV-2 is associated mainly with diseases of the urogenital tract. In the immunocompetent host, viral replication is usually confined to cutaneous and mucocutaneous sites, invasion of subcutaneous tissues being impeded by an early onset of non-specific defence mechanisms. These are rapidly complemented by the specific, mainly cellular, immune response. PATIENTS: Epithelial dendritic keratitis is the first symptomatic clinical finding, and after several recurrences, the corneal stroma may become involved. This condition of herpetic stromal keratitis (HSK), which, in contrast to the epithelial one, is believed to be directed by a predominantly immunopathological process, is one of the leading causes of infectious blindness in developed countries. RESULTS: The mechanisms underlying HSK, and the establishment of viral latency and reactivation are poorly understood. But on the basis of studies with mice as well as clinical immunohistological observations, evidence is now accumulating in support of a cell-mediated mechanism being responsible for corneal destruction. CONCLUSION: Our present knowledge of the pathogenesis of herpetic keratitis is incomplete. The different pathophysiological aspects reflecting our current understanding, such as that of a virally induced autoimmune disease, form the basis of accepted clinical treatment concepts.