Michael Küchle

Pseudoexfoliation syndrome for the comprehensive ophthalmologist. Intraocular and systemic manifestations.

BACKGROUND Renewed interest in pseudoexfoliation syndrome (PEX) may be attributed to an increased awareness of many clinical risks not only for open-angle glaucoma and its recent recognition as a generalized disorder. This review summarizes the range of intraocular and extraocular manifestations. Involvement of all tissues of the anterior segment of the eye results in a spectrum of intraocular complications that have management implication for all practicing ophthalmologists. DESIGN The study design was a review. METHODS Clinical diagnosis depends on biomicroscopy, biocytology, and laser-tyndallometry. Laboratory research methods range from light and electron microscopy, to immunohistochemical and molecular biologic approaches. OBSERVATIONS Clinical-histopathologic correlations focus on the involvement of lens (PEX-phacopathy), zonular apparatus (zonulopathy), ciliary body (cyclopathy), iris (iridopathy), trabecular meshwork (trabeculopathy), and cornea (corneal endotheliopathy) leading to the following complications: (1) open-angle glaucoma as well as angle-closure glaucoma due to pupillary and ciliary block; (2) phacodonesis, lens dislocation, and increased incidence of vitreous loss in extracapsular cataract surgery caused by alterations of the zonular apparatus and its insertion into the ciliary body and lens; (3) blood-aqueous barrier breakdown (pseudouveitis), anterior chamber hypoxia, iris stromal hemorrhage, pigment epithelial melanin dispersion, poor or asymmetric pupillary dilatation, and formation of posterior synechiae due to involvement of all cell populations of the iris; and (4) early diffuse corneal endothelial decompensation explained by a damaged and numerically reduced endothelium. CONCLUSIONS In view of the multitude of clinical complications, PEX is of relevance to comprehensive ophthalmologists, including specialists in glaucoma, cataract, cornea, neuro-ophthalmology, and retina. Special attention to the risks associated with PEX is advised before, during, and after surgery.

Nonmechanical corneal trephination with the excimer laser improves outcome after penetrating keratoplasty1

OBJECTIVE To assess the impact of nonmechanical trephination on the outcome after penetrating keratoplasty (PK). DESIGN Prospective, randomized, cross-sectional, clinical, single-center study. PATIENTS A total of 179 eyes of 76 females and 103 males, mean age at the time of surgery 50.6 +/- 18.5 (range, 15-83) years. Inclusion criteria were (1) time interval from October 1992 to December 1997; (2) one surgeon (GOHN); (3) primary central PK; (4) Fuchs dystrophy (diameter, 7.5 mm) or keratoconus (diameter, 8.0 mm); (5) graft oversize, 0.1 mm; (6) no previous intraocular surgery; and (7) 16-bite double-running diagonal suture. INTERVENTION In a randomized fashion, eyes were assigned either to trephination with the 193-nm Meditec excimer laser (manually guided beam in patients, automated rotation device of artificial anterior chamber in donors) along metal masks with eight orientation teeth/notches (EXCIMER: 53 keratoconus, 35 Fuchs dystrophy; mean follow-up, 37 +/- 16 months) or with a hand-held motor trephine (Microkeratron; Geuder) ( CONTROL 53 keratoconus, 38 Fuchs dystrophy; mean follow-up, 38 +/- 14 months). Subjective refractometry (trial glasses), standard keratometry (Zeiss), and corneal topography analysis (TMS-1; Tomey) were performed before surgery, before removal of the first suture (15.2 +/- 4.2 months), and after removal of the second suture (21.4 +/- 5.6 months). MAIN OUTCOME MEASURES Keratometric and topographic net astigmatism as well as refractive cylinder; keratometric and topographic central power; best-corrected visual acuity (VA); surface regularity index (SRI), surface asymmetry index (SAI), and potential visual acuity (PVA) of the TMS-1. RESULTS Before suture removal, mean refractive/keratometric/topographic astigmatism did not differ significantly between EXCIMER (2.5 +/- 1.8 diopters [D]/3.4 +/- 2.8 D/4.7 +/- 3.1 D) and CONTROL groups (3.0 +/- 1.8 D/3.7 +/- 2.4 D/4.3 +/- 2.1 D). After suture removal, respective values were significantly lower in the EXCIMER group (2.8 +/- 2.0 D/3.0 +/- 2.1 D/3.8 +/- 2.6 D) than in the CONTROL group (4.2 +/- 2.4 D/6.1 +/- 2.7 D/6.7 +/- 3.1 D) (P < 0.0009). In the EXCIMER versus CONTROL group, mean VA increased from 20/100 versus 20/111 (P > 0.05) before surgery, to 20/31 versus 20/38 before (P = 0.001) and to 20/28 versus 20/39 (P < 0.00001) after suture removal. Mean spherical equivalent was significantly less myopic in the EXCIMER group before (-0.9 +/- 3.6 D vs. -2.6 +/- 3.4 D) (P = 0.01) and after suture removal (-1.4 +/- 3.1 D vs. -2.4 +/- 3.5 D) (P = 0.02). Mean SRI (P = 0.04) and PVA (P = 0.007) were significantly more favorable in the EXCIMER versus CONTROL group after suture removal (0.91 +/- 0.45 and 0.82 +/- 0.15 vs. 1.05 +/- 0.46 and 0.73 +/- 0.18). CONCLUSIONS Postkeratoplasty results seem to be superior using nonmechanical excimer laser trephination. Thus, this methodology is recommended as the procedure of first choice in avascular corneal pathologies requiring PK.

Measurement of accommodation after implantation of an accommodating posterior chamber intraocular lens.

Purpose: To analyze techniques of measuring accommodation after implantation of an accommodating posterior chamber intraocular lens (PC IOL). Setting: Department of Ophthalmology and University Eye Hospital, University Erlangen‐Nürnberg, Erlangen, Germany. Methods: This prospective study analyzed 23 eyes of 23 patients (aged 41 to 87 years) after cataract surgery and PC IOL implantation (1 CU®, HumanOptics) 4 weeks and 3 and 6 months after surgery. The results were compared to those in an age‐matched control group (n = 20) 6 months after surgery. The following methods were used to measure accommodation: dynamic with objective techniques (PlusOptix PowerRefractor® videorefractometry, streak retinoscopy) and subjective techniques (subjective near point [push‐up test, accommodometer], defocusing); static with pharmacologic stimulation after pilocarpine 2% eyedrops directly (conventional refractometry); indirectly (change in the anterior chamber depth [ACD] with Zeiss IOLMaster®). Results: Results at 6 months, given as mean ± SD (range), in the study and control groups, respectively, were as follows: near visual acuity (Birkhäuser reading charts at 35 cm) with distance correction, 0.32 ± 0.11 (0.20 to 0.60) and 0.14 ± 0.10 (0.05 to 0.30); accommodation amplitude (diopters) by PowerRefractor, 1.00 ± 0.44 (0.75 to 2.13) and 0.35 ± 0.26 (0.10 to 0.65), by retinoscopy, 0.99 ± 0.48 (0.13 to 2.00) and 0.24 ± 0.21 (–0.13 to +0.75), by subjective near point, 1.60 ± 0.55 (0.50 to 2.56) and 0.42 ± 0.25 (0.00 to 0.75), and by defocusing, 1.46 ± 0.53 (1.00 to −2.50) and 0.55 ± 0.33 (0.25 to 0.87). The mean ACD decrease (mm) was 0.78 ± 0.12 (0.49 to 1.91) and 0.16 ± 0.09 (0.00 to 0.34) after pilocarpine 2% eyedrops, indicating a mean accommodation of 1.40 D and 0.29 D, respectively, based on Gullstrands model eye (P = .001). The lowest fluctuation between follow‐ups was with the subjective near point and the defocusing techniques followed by ACD decrease with the IOLMaster. Conclusions: Accommodation after implantation of an accommodating PC IOL should be assessed with several techniques, including subjective and objective, to differentiate true pseudophakic accommodation from pseudoaccommodation. Researchers should be aware of the different variability and consistency of measurements with each technique over time.

Immunohistochemical localization of vascular endothelial growth factor, transforming growth factor alpha, and transforming growth factor beta1 in human corneas with neovascularization.

Purpose. To analyze presence and distribution of vascular endothelial growth factor (VEGF), transforming growth factor (TGF)&agr;, and TGF&bgr;1 in human corneas with neovascularization due to different corneal diseases. Methods. Indirect immunohistochemistry for VEGF, TGF&agr;, and TGF&bgr;1 was performed on paraffin-embedded corneas obtained by keratoplasty. Corneas from each of the four main groups of histopathologic diagnoses associated with corneal neovascularization were analyzed (scarring after keratitis, graft rejection/insufficiency, acute necrotizing keratitis, scarring after mechanical/chemical injury). Subclassification of inflammatory infiltrates was done using immunohistochemistry for CD3 (T-lymphocytes) and CD68 (macrophages). Results. The analyzed angiogenic factors were detectable in corneas from all four histopathologic groups in a similar distribution; capillary endothelial cells, stromal and intravascular inflammatory cells (T-lymphocytes, macrophages), and basal corneal epithelial cells stained positive for the tested angiogenic factors. Conclusion. The angiogenic factors VEGF, TGF&agr;, and TGF&bgr;1 are detectable in human corneas with neovascularization. Their distribution is quite uniform in different corneal diseases, resulting in corneal angiogenesis. An antiangiogenic therapy inhibiting corneal neovascularization by antagonizing angiogenic factors would have to counteract several angiogenic factors.

Angiogenesis in corneal diseases: histopathologic evaluation of 254 human corneal buttons with neovascularization.

PURPOSE Angiogenesis in corneal diseases can necessitate corneal transplantation and induce graft rejection. The aim of this study was to find out the histopathologic prevalence of angiogenesis in human corneas removed during keratoplasty, to establish the histopathologic diagnoses most commonly associated with angiogenesis, and to evaluate the anatomic location of new corneal vessels. METHODS Corneal buttons (2,557) after keratoplasty were sent to and analyzed in our ophthalmopathology laboratory between 1992 and 1996. Of these, 1,278 full-thickness and lamellar corneal buttons were randomly retrieved and evaluated in this study. RESULTS Of 1,278 human corneal buttons obtained by keratoplasty, 254 (19.9%) showed angiogenesis. Associated histopathologic diagnoses were (a) scarring after keratitis (109, 45.4%); (b) graft rejection and insufficiency (73, 30.4%); (c) acute necrotizing ulcerative keratitis (30, 12.5%); and (d) scarring after mechanical or chemical injuries (28, 11.7%). Histopathologically, new vessels were usually associated with corneal edema or inflammatory cells or both (76%). The most common locations of new vessels were the upper and middle third of the corneal stroma. Only 11% of new vessels were located solely in the deep stromal layers. CONCLUSION Angiogenesis is a common histopathologic feature of corneal diseases leading to corneal transplantation and was found in 19.9% of excised human corneal buttons. Systemic or topical antiangiogenic therapy could reduce the need for corneal transplantation and retransplantation.

Implantation of a new accommodative posterior chamber intraocular lens.

PURPOSE A new, potentially accommodative posterior chamber lens (PCIOL) was designed based on principles elaborated by Hanna using finite element computer simulation methods. We report 3-month postoperative results in patients. METHODS In a prospective study, 12 eyes of 12 patients (age 45 to 87 yr) underwent phacoemulsification for cataracts and PCIOL implantation. The PCIOL, 1 CU, has haptics designed for anterior optic movement following ciliary muscle contraction. Patients were examined postoperatively after 1 and 2 days, 1, 2 and 6 weeks, and 3 months, and results were compared with a control group of 12 eyes that received standard PMMA or acrylic PCIOLs. RESULTS Surgery was uncomplicated and all PCIOLs were well-tolerated and stable with good centration in the capsular bag. The results were (mean +/- SD [range] and median; 1 CU versus control PCIOL): near visual acuity (Birkhäuser reading chart at 35 cm) with best distance correction 0.34 +/- 0.17 (0.2 to 0.6), 0.3 (J10-J1, median J7) versus 0.15 +/- 0.07 (0.1 to 0.3), 0.15 (J16-J7, median J13), P=.001; subjective near point 59 +/- 10 cm (40 to 100 cm), 53.5 cm versus 93 +/- 20 cm (64 to 128 cm), 86 cm, P=.004; retinoscopic accommodative range 1.2 +/- 0.4 D (0.63 to 1.5 D), 1.2 D versus 0.2 +/- 0.19 D (-0.25 to 0.5 D), 0.25 D, P < .001; decrease of anterior chamber depth after 2% pilocarpine 0.63 +/- 0.16 mm (0.40 to 0.91 mm), 0.63 mm versus 0.15 +/- 0.05 mm (0.08 to 0.20 mm), 0.17 mm, P < .001. CONCLUSIONS The new PCIOL appears to be safe at short to medium term. Our results indicate pseudophakic accommodation secondary to focus shift with this PCIOL. Additional larger and long-term studies are necessary for exact evaluation of safety and accommodative power of this new PCIOL.

The Blood-Aqueous Barrier in Eyes with Pseudoexf oliation Syndrome

UNLABELLED Eyes with pseudoexfoliation syndrome (PEX) frequently show clinical signs of impairment of the blood-aqueous barrier. Herein we give an overview of recent studies that analyzed the blood-aqueous barrier in eyes with PEX. METHODS The authors review and summarize recent studies including quantification of aqueous flare in eyes with PEX using the laser flare cell meter (LFCM; Kowa FC-1000) in comparison with normal eyes and eyes with primary open-angle glaucoma (POAG), quantification of aqueous flare in eyes with PEX with and without secondary open-angle glaucoma (SOAG), and quantitative biochemical determination of total aqueous protein concentration in PEX eyes. In addition, studies of noninvasive quantification of the blood-aqueous barrier breakdown following trabeculectomy and following phacoemulsification with intraocular lens implantation in eyes with and without PEX are reviewed. RESULTS In eyes with manifest PEX, both aqueous flare and aqueous protein concentration were significantly increased in comparison with normal control eyes and eyes with POAG. Flare values in PEX eyes with SOAG were not significantly different from flare values in PEX eyes without SOAG. Following trabeculectomy as well as following cataract surgery, breakdown of the blood-aqueous barrier as determined by quantification of aqueous flare was significantly higher in eyes with PEX than in eyes without PEX. CONCLUSIONS Impairment of the blood-aqueous barrier with increase in aqueous protein concentration is a feature of PEX and may be quantified both by flare measurement and by biochemical protein determination. The extensive blood-aqueous barrier breakdown in eyes with PEX following intraocular surgery is an important risk factor for early or late postoperative complications. The alterations of the blood-aqueous barrier should be considered in the medical and surgical treatment of eyes with PEX.

Anterior chamber depth and complications during cataract surgery in eyes with pseudoexfoliation syndrome

PURPOSE To look for associations of preoperative A-scan ultrasound ocular dimensions with complications during phacoemulsification in eyes with pseudoexfoliation. METHODS A total of 174 eyes with pseudoexfoliation of 135 patients undergoing planned cataract surgery were included in a prognostic study based on the review of a clinical database. Preoperatively, A-scan ultrasound examination with measurement of anterior chamber depth, lens thickness, and total axial length was performed. Phacoemulsification with implantation of a posterior chamber intraocular lens was performed by a total of five surgeons. Intraoperative complications (zonular dialysis and/or vitreous loss) were correlated with preoperative findings including ultrasound dimensions. Multivariate logistic regression analysis with a generalized estimating equations method was used for statistical analysis. RESULTS Intraoperative complications occurred in 12 eyes (6.9%) of 11 patients. The anterior chamber was significantly shallower in eyes with than in eyes without complications (mean, 2.36 +/- 0.44 mm vs 2.74 +/- 0.52 mm; P =.013). The differences in lens thickness (4.93 +/- 0.55 mm vs 4.72 +/- 0.54 mm; P =.30) and the differences in axial length (22.92 +/- 1.09 mm vs 23.66 +/- 1.36 mm; P =.07) between the two groups did not reach statistical significance. In eyes with pseudoexfoliation, an anterior chamber depth of less than 2.5 mm was associated with a risk of 13.4% for intraoperative complications compared with an overall incidence of intraoperative complications of 6.9% and an incidence of 2.8% for an anterior chamber depth of 2.5 mm or more. CONCLUSIONS A small anterior chamber depth may indicate zonular instability in eyes with pseudoexfoliation syndrome and should alert the cataract surgeon to the possibility of intraoperative complications.

Pseudoexfoliation syndrome: pathological manifestations of relevance to intraocular surgery

Pseudoexfoliation syndrome (PEX) is a common ocular condition often associated with the need for intraocular surgery. Although results of cataract and glaucoma filtering surgery in eyes with PEX in the early stages of the disease may be comparable to those in eyes without PEX, in the later stages morbidity is significantly increased due to periocular surgical complications and the outcome is worse. Surgical and postoperative difficulties are often multifactorial and are directly related to the pathological changes of PEX on intraocular structures. Recent years have seen a large increase in the understanding of the effects of PEX on the various ocular tissues. Although the visible areas of the anterior capsule are most obviously involved, this is only a small part of the picture and of least significance. Biomicroscopically invisible changes of the zonules and their attachments are of greatest consequence. There is also distinct, often active, involvement of almost all tissues of the anterior segment of the eye, many of which have important implications for the anterior segment surgeon including iridopathy, iris vasculopathy (including persistent breakdown of the blood−aqueous barrier and anterior segment hypoxia), ciliary body involvement and keratopathy. Trabecular dysfunction is evident by the deposition of PEX material derived from both in situ and extra‐trabecular production as well as protein and melanin deposition. These changes should be kept in mind by all intraocular surgeons as a source of potential difficulties in the perioperative period. Additionally, in light of these changes, patients need to be given realistic expectations regarding the increased risk of complications and more prolonged expected recovery time. In this short review, current reports relating to PEX pathological changes of practical interest to the intraocular surgeon are summarized.

Pseudoexfoliation syndrome and secondary cataract

AIM/BACKGROUND The pseudoexfoliation (PEX) syndrome is frequently associated with impairment of the blood-aqueous barrier. This study analysed if this might stimulate secondary cataract following cataract extraction. METHODS This historical cohort study included 197 eyes of 197 patients (99 with and 98 without PEX) that underwent extracapsular cataract extraction with posterior chamber lens implantation (PMMA optic) between 1985 and 1991. Secondary cataract was defined as opacification of the axial posterior capsule and decrease of visual acuity by two or more lines. Mean follow up was 23.8 months. For statistical analysis, the Kaplan–Meier method and multivariate Cox regression analysis were used. RESULTS Secondary cataract was observed within 24 months in 35% (SD 7%) of all eyes, and was significantly more frequent in eyes with PEX (45 (11)%) than in eyes without PEX (24 (9)%, p<0.03). Eyes with diabetes mellitus (n=32) showed a significantly lower frequency of secondary cataract (11 (11)%) than eyes without diabetes mellitus (39 (8)%, p<0.01). The influences of sex, open angle glaucoma, type of cataract, surgeon, positioning of IOL, and phacoemulsification versus nuclear expression on secondary cataract did not reach statistical significance. CONCLUSION The higher frequency of secondary cataract could be considered as another potential complication of cataract surgery in eyes with PEX.