[Perspectives of excimer laser-assisted keratoplasty]. / Perspektiven der Excimerlaser-Trepanation für die Keratoplastik.

BACKGROUND AND PURPOSE: The purpose of this paper is to demonstrate the evolution of laser keratoplasty and to outline the potential future perspectives of this technique. METHODS: For non-contact donor trephination from the epithelial side an artificial anterior chamber has been used. Since 1989 more than 3,300 penetrating keratoplasty operations (PKP) have been performed successfully with the Zeiss-Meditec MEL60® excimer laser in Erlangen and Homburg/Saar. RESULTS: Prospective clinical studies have shown that the technique of non-contact excimer laser PKP improves donor and recipient decentration, reduces vertical tilt and horizontal torsion of the graft in the recipient bed, thus resulting in significantly less all-sutures-out keratometric astigmatism, higher regularity of the topography and better visual acuity. Besides less blood-aqueous barrier breakdown during the early postoperative course after PKP, excimer laser trephination does not induce cataract formation and does not impair the graft endothelium. Likewise, the rate of immunological graft rejections is not adversely affected by the excimer laser. In addition, trephination of an instable cornea is facilitated. CONCLUSIONS: Because of undisputed clinical advantages, especially in eyes with keratoconus, excimer laser trephination with orientation teeth/notches is still favored in Homburg/Saar in daily practice. The femtosecond laser (FSL)-assisted keratoplasty technique is very exciting but a prospective randomized study is required to determine potential benefits over excimer laser PKP.

[Accuracy of IOL power prediction in cataract surgery after penetrating keratoplasty--retrospective study of 72 eyes]. / Treffsicherheit der Kunstlinsenberechnung bei Katarakt-Operation nach perforierender Keratoplastik--retrospektive Studie an 72 Augen.

BACKGROUND: In concomitant cataract surgery and penetrating keratoplasty (PKP), the sequential procedure is supposed to have a higher accuracy in calculation of the intraocular lens (IOL) power compared to the triple procedure. The purpose of this study was to evaluate the refractive results of cataract surgery in patients after PKP. MATERIALS AND METHODS: Our retrospective study included 72 operations on 65 patients. In 35 eyes (group 1, G 1), all corneal sutures had been removed before cataract surgery (median time interval after PKP 3.1 years), while in 37 eyes (group 2, G 2) corneal sutures were in place but removed intra- or postoperatively (median time interval after PKP 1.5 years). Mean age of the patients (65 / 67 years), mean target refraction (-1.8 diopters, D), and mean follow-up interval (2.9 / 3.4 years) were comparable in G1 / G2. Pre- and postoperatively refraction, keratometry, and best corrected visual acuity were recorded. Main outcome measures included the deviation of the spherical equivalent of the real refraction from the target refraction after cataract surgery. RESULTS: In G1 / G2 median visual acuity increased from preoperatively 0.2 / 0.15 to 0.6 / 0.5 after a follow-up period of 3 years on average. Mean deviation from target refraction was -0.3 ± 2.2 (-4.95 to + 3.15) D in G 1 and -0.4 ± 3.0 (-7.3 to + 7.25) D in G 2. After cataract surgery, the steepening of the cornea on average was significantly less in G 1 (0.5 ± 1.6 D) than it was in G 2 (3.3 ± 2.1 D; p = 0.003). CONCLUSIONS: Although the mean deviation from target refraction is minimal after cataract surgery following PKP, our results indicate a high level of variability. If corneal sutures have been completely removed before biometry, the accuracy of the IOL power calculation seems to be better.

Increased homocysteine levels in tear fluid of patients with primary open-angle glaucoma.

AIMS: We assessed homocysteine (Hcy) levels in tear fluid and plasma of patients with primary open-angle glaucoma (POAG). We determined the association between Hcy levels, dry eye syndrome and B vitamin status. METHODS: This prospective case-control study included 36 patients with POAG and 36 controls. Hcy concentrations were measured by high-performance liquid chromatography. RESULTS: Patients with POAG had significantly higher mean Hcy levels both in tear fluid (205 +/- 84 nmol/l; p < 0.001, t test) and in plasma (13.43 +/- 3.53 micromol/l; p = 0.001, t test) than control subjects (130 +/- 53 nmol/l and 10.50 +/- 3.33 micromol/l, respectively). Hcy in tear fluid was significantly correlated with plasma Hcy in POAG patients (r = 0.459; p = 0.005, Pearson's correlation), but not in controls (r = 0.068; p = 0.695). POAG patients with dry eye disease had significantly higher Hcy levels both in tear fluid and plasma than POAG patients without dry eye disease. There was no association between Hcy levels and B vitamin status in subjects with POAG. CONCLUSIONS: The study suggests increased Hcy levels in tear fluid and plasma of patients with POAG. Elevated Hcy levels might be a risk factor for POAG and dry eye syndrome in subjects with glaucoma.

Aggressive metastasising adenocarcinoma of the retinal pigment epithelium with trisomy 21.

This case report describes a 37-year-old man with a blind eye with opaque media. Histopathology revealed an aggressive adenocarcinoma of the retinal pigment epithelium with marked invasion of the choroid, retina, sclera and--not previously reported--the orbital and cranial optic nerve and subarachnoid space. The tumour seeded into the lumbar spinal-cord space. Metastatic foci--not in continuity with the primary process--developed in the parietal lobe and cerebellopontine angle. Adenocarcinoma of the retinal pigment epithelium, which occurs rarely in longstanding blind eyes, may exhibit aggressive behaviour with life-threatening risk of metastatic spread.

Vitamin deficiency and hyperhomocysteinemia in pseudoexfoliation glaucoma.

Pseudoexfoliation syndrome (PEX) is a systemic disorder characterized by the deposition of an abnormal fibrillar material in ocular and various extraocular tissues. It represents the most common identifiable cause of glaucoma (PEX glaucoma = PEXG). Due to similar pathogenetic mechanisms, glaucoma has been called "ocular Alzheimer's disease". PEXG and Alzheimer's disease share common associations such as the higher prevalence of hyperhomocysteinemia in both disorders. In order to investigate the cause of hyperhomocysteinemia in PEXG, we evaluated B-vitamin levels (folate, B12, B6) and their associations with homocysteine (Hcy) in plasma of 70 PEXG patients and 70 control subjects. Folate, vitamin B12 and B6 levels were significantly decreased and associated with elevated Hcy levels in PEXG. Low B-vitamin levels in PEX might also help explain, at least in part, the higher prevalence of B-vitamin deficiency in disorders associated with PEX such as Alzhemier's disease.

Homocysteine levels in aqueous humor and plasma of patients with primary open-angle glaucoma.

We determined homocysteine (Hcy) levels in aqueous humor (AH) and plasma and their association with B-vitamin levels in patients with primary open-angle glaucoma (POAG) and controls. Both AH Hcy and plasma Hcy levels were significantly increased in POAG, and elevation of AH Hcy and plasma Hcy was a significant risk factor for POAG. In contrast to controls, neither plasma nor AH Hcy of POAG patients demonstrated a significant association with important non-genetic determinants of elevated Hcy such as low B-vitamin levels, increasing age and caffeine consumption. Considering that Hcy is a neurotoxin that induces apoptotic retinal ganglion cell death via stimulation of the N-methyl-D-asparate (NMDA) receptor, increased Hcy concentrations in AH and plasma might contribute to the optic nerve damage in POAG.

[High-dose 106Ruthenium plaque brachytherapy for posterior uveal melanoma. A clinico-pathologic study]. / Hochdosisbrachytherapie des malignen Aderhaut- und Ziliarkörpermelanoms mit 106Ruthenium. Eine klinisch-pathologische Studie.

BACKGROUND: The purpose of this study was to report the multifactorial results of high-dose (106)Ruthenium plaque brachytherapy for (cilio-)choroidal melanoma and to confirm them by histological examinations. PATIENTS AND METHODS: 100 patients with choroidal or ciliochoroidal melanoma treated by high-dose 106Ruthenium plaque brachytherapy were followed-up for 5 years. 12 secondary enucleated eyes were compared to a non-irradiated matched group by light microscopy. RESULTS: The 5-year local tumour control rate was 93%, the 5-year survival rate 91%. Late radiogenic side effects occured as a retinopathy in 13%, as an optic neuropathy in 5% and as a secondary glaucoma in 3% of the patients. 14% had to be enucleated, 10% developed metastases. The histopathologic examination revealed significantly higher degrees of necrosis (p=0,041), balloon cell degeneration (p=0,025) and fibrosis (p<0,001) in the irradiated melanomas than in the control tumours. CONCLUSION: High-dose 106Ruthenium plaque brachytherapy turned out to be an effective treatment procedure for posterior uveal melanoma (not exceeding a prominence of 5,5 mm) with a high rate of local tumour control and a low rate of side effects.

[The penetrating keratoplasty. A 100-year success story]. / Die perforierende Keratoplastik. Eine 100-jährige Erfolgsgeschichte.

Ten precautions for prophylaxis of astigmatism in penetrating keratoplasty are recommended:1. The attempt should be made to determine donor topography for exclusion of previous refractive surgery, keratoconus/high astigmatism, and to allow for "harmonization" of donor and recipient topography.2. Donor and recipient trephination should be performed from the epithelial side with the same system, which is the prerequisite for congruent cut surfaces and angles in donor and recipient. For this purpose an artificial anterior chamber is used for donor trephination.3. Orientation structures in donor and host facilitate the correct placement of the first four or eight cardinal sutures to avoid horizontal torsion.4.A measurable improvement seems to be possible, using the Krumeich guided trephine system (GTS), the second generation Hanna trephine, and the Erlangen technique of nonmechanical trephination with the excimer laser.5. Horizontal positioning of the head and limbal plane are indispensable for state-of-the-art PKP surgery in order to avoid decentration, vertical tilt, and horizontal torsion.6. Graft size should be adjusted individually ("as large as possible, as small as necessary").7. Limbal centration should be preferred over pupil centration (especially in keratoconus).8. Excessive graft over- or undersize should be avoided to prevent stretching or compression of peripheral donor tissue.9. As long as Bowman's layer is intact a double running cross-stitch suture (according to Hoffmann) is preferred since it results in higher topographic regularity, earlier visual rehabilitation, and less suture loosening requiring only rarely suture replacement.10.Intraoperative keratoscopy should be applied after removal of lid specula and fixation sutures.

[Results of the first 1,000 consecutive elective nonmechanical keratoplasties using the excimer laser. A prospective study over more than 12 years]. / Ergebnisse der ersten 1.000 konsekutiven elektiven nichtmechanischen Keratoplastiken mit dem Excimerlaser. Eine prospektive Studie über mehr als 12 Jahre.

BACKGROUND AND PURPOSE: The purpose of this prospective clinical cross-sectional study was to analyse indications, intraoperative, perioperative and postoperative pecularities and complications as well as postoperative functional and morphologic results of the first 1000 consecutive elective round laser keratoplasties. PATIENTS AND METHODS: The age of the 480 females and 520 males (362 x keratoconus), who had been operated on between 07/1989 and 04/2002 ranged from 20 to 92 years (mean 55+/-19). A total of 6 microsurgeons performed 718 x PK only, 222 x a triple procedure and 60 x additional IOL manoeuvres. Recipient and donor trephinations were accomplished with an 193 nm excimer laser (Carl Zeiss Meditec, Jena, Germany) from the epithelial side. RESULTS: In 895 eyes with perioperative corneal erosion, epithelial healing took not more than 3 days in half of cases. During a follow-up period of 1.9+/-1.5 years, in 35 eyes episodes of acute diffuse (8 irreversible) and in 12 eyes episodes of chronic focal (5 irreversible) endothelial immunologic graft reactions (4.7%) occurred between 6 weeks and 4.7 years after PK. Before/after suture removal, median values of astigmatism were 1.5 diopters (D)/2.5 D refractive, 3.0 D/3.3 D keratometric, and 4.0 D/4.2 D topographic. Best-corrected visual acuity was 0.50/0.60, respectively. CONCLUSIONS: More than 12 years of experience with this new technique indicate that besides optical advantages, nonmechanical trephination does not cause intraoperative or postoperative disadvantages for the patient. Under standardised surgical conditions a massive increase of astigmatism after suture removal seems to be avoidable with laser trephination in most cases due to reduction of decentration,"vertical tilt" and especially "horizontal torsion".

[Phototherapeutic keratectomy (o-PTK) with 193 nm excimer laser for superficial corneal scars. Prospective long-term results of 31 consecutive operations]. / Phototherapeutische Keratektomie (o-PTK) mittels 193-nm-Excimerlaser bei oberflächlichen HornhautnarbenProspektive Langzeitergebnisse von 31 konsekutiven Eingriffen.

PURPOSE: To investigate the functional and morphological long-term outcome of phototherapeutic keratectomy (PTK) for superficial corneal scars of varying origin. PATIENTS AND METHODS: Between 1989 and 11/2002, 317 PTKs were performed in Erlangen, of which 31 consecutive procedures were assessed in this prospective study. The intended laser ablation depth after epithelial debridement and pannectomy varied from 12 to 150 microm. We used the slit-scanning-mode (Carl Zeiss Meditec AG) with a repetition rate of 20/s or 25/s, a pulse energy of 14.5 mJ (median) and a pulse rate of 2565+/-2036 (222-6962). In most cases a 6.0 mm metal mask was used to protect peripheral Bowman's layer. RESULTS: After a mean follow-up of 2.0+/-1.9 (maximum 6.9) years, best-corrected visual acuity increased from preoperatively 0.3+/-0.2 to 0.5+/-0.3 (increase 87%, no change 10%, decrease 3%). Corneal surface topography regularized significantly (p=0.02). The spherical equivalent increased only slightly from -0.4+/-2.5 D preoperatively to 0.2+/-2.9 D postoperatively. Likewise, mean keratometric central power did not change significantly. In 10 eyes the maximum postoperative haze was mild, in 4 eyes moderate, and there was only one recurrent scar after delayed epithelial healing following epidemic keratoconjunctivitis. CONCLUSIONS: In superficial corneal scars of varying origin an o-PTK using the 193 nm excimer laser can moderately increase visual acuity in most cases. Therefore, a lamellar or penetrating keratoplasty might be avoided.

Q-switched erbium:YAG laser corneal trephination: thermal damage in corneal stroma and cut regularity of nonmechanical Q-switched erbium:YAG laser corneal trephination for penetrating keratoplasty.

PURPOSE: To assess stromal thermal damage and cut regularity induced by nonmechanical Q-switched Er:YAG laser corneal trephination for penetrating keratoplasty. METHODS: Corneal trephination was performed in 80 enucleated porcine eyes by Q-switched (2.94-microm) Er:YAG laser, along with donor and recipient masks made of metal or ceramic. All combinations of 0.65- or 0.96-mm spot diameter and 45- or 50-mJ/pulse energy setting were used with each of the masks at a 5-Hz repetition rate. Corneas were processed for histologic examinations. Stromal thermal damage was quantified on PAS-stained slides, and cut regularity was assessed semiquantitatively on a scale from 0 (regular) to 3 (highly irregular). Transmission electron microscopy and scanning electron microscopy were performed on selected specimens. RESULTS: The least thermal damage (mean +/- SD = 6.2 +/- 0.7 microm) was found in the donor ceramic group with 50-mJ/pulse energy and 0.65-mm spot diameter, while the best regularity of the cut (1.2 +/- 0.4) was found in the donor ceramic group with 45-mJ pulse energy and 0.65-mm spot diameter. Thermal damage was less pronounced in donor than in recipient corneas (P < 0.01). Smaller spot diameter (0.65 mm) led to less thermal damage (P < 0.01) than the use of a 0.96-mm spot diameter. The differences in thermal damage between ceramic and metal masks were minimal. CONCLUSIONS: After Q-switched Er:YAG laser corneal trephination for nonmechanical penetrating keratoplasty, reproducible high cut regularity and low concomitant thermal damage were observed. This is an encouraging finding in the search for a nonmechanical trephine for penetrating keratoplasty combining high precision and low cost.

[Classification of ocular surface disease. Part 1]. / Klassifikation der Erkrankungen der Augenoberfläche. Teil I.

The ocular surface consists of the lid margin, conjunctiva and cornea which together with the tear system represent a functional entity. The diagnosis of ocular surface disease can be very difficult due to the similarity of various disease entities. The classification should be made on the pathological and pathophysiological characteristics of ocular surface disease. The first part of the classification comprises diseases of the lid margin, the tear system as well as diseases of the conjunctiva. Both the clinical presentation as well as the underlying pathophysiological and pathological characteristics of the most important ocular surface diseases are reviewed.

[Management of conjunctival malignant melanoma associated with primary acquired melanosis (PAM) using 0.02% mitomycin C eyedrops]. / Therapie maligner Melanome der Konjunktiva bei primär erworbener Melanose (PEM) mit Mitomycin-C-0,02%-Augentropfen.

BACKGROUND: The therapy of malignant diseases of the conjunctiva with local chemotherapy is an extension of the therapeutic options in this field. We report on our experience in the therapy of malignant melanomas of the conjunctiva associated with primary acquired melanosis (PAM). METHODS AND PATIENTS: Between March 1998 and April 2001, 13 patients with malignant melanoma of the conjunctiva associated with PAM (6 female; 7 male; mean age 57+/-13 years) were treated with local chemotherapy. The tumor was classified as stage pT2 (pN0, pM0) in seven patients, stage pT3 (pN0, pM0) in three patients and in the remaining three patients the lid was involved in the malignant process (pT4, pN0, pM0). Local chemotherapy (mitomycin C 0.02% eyedrops 5 times a day) was applied after incisional biopsies in 2 cycles for 14 days with a 14-day break. In 4 patients a third cycle was included. RESULTS: Regression of the tumor was observed after completion of the therapy in all cases. Severe ocular or systemic secondary effects were not seen in our patients. Nine patients were without recurrence within the follow-up time. In three patients, a recurrence of the disease was observed. In these cases, the eyelid was involved in the process. CONCLUSION: Local chemotherapy with mitomycin C is a useful option in the treatment of malignant melanomas of the conjunctiva associated with PAM if the tumor stage is pT3 or less. From our point of view the combination with incisional biopsy is of great benefit. Prognosis of conjunctival malignant melanomas involving the lid margin (pT4) is poor.

[Impact of an Er:YAG laser beam control on cut quality of non-mechanical corneal trepanation for penetrating keratoplasty]. / Einfluss der Er:YAG-Laserstrahlführung auf die Schnittqualität der nichtmechanischen Hornhauttrepanation für die perforierende Keratoplastik.

BACKGROUND: Results of non-mechanical corneal trepanation using the excimer laser enhance the morphological and functional results for penetrating keratoplasty. Searching for alternative laser sources we assessed the impact of an automatic laser beam control for the Er:YAG solid-state laser on the cut performance and thermal damage zone in non-mechanical corneal trepanation. METHODS: We compared the cut quality of A) a manually guided laser beam, B) a semiautomatically guided laser beam and C) a fully PC-controlled laser beam positioning system (q-switched, repetition rate 5 Hz, pulse energy 65 mJ, spot size 0.7 mm) along slit aperture masks on 28 rabbit eyes using macroscopic images and histological sections (PAS staining). RESULTS: The manually guided laser beam control (A) induced the broadest thermal damage zone in the corneal stroma (19.3+/-8.7 microm) compared to the semi-automatic mode (B) (8.8+/-3.0 microm, p=0.03) and the PC-controlled laser beam control (C) (7.0+/-3.0 microm, p=0.016). CONCLUSION: The fully automatic PC-controlled laser beam positioning system for the Er:YAG solid-state laser with a small spot size and fixed low repetition rate allows a precise laser beam guidance and a significant enhancement of the cut performance compared to a manual laser beam control via micromanipulator in experimental nonmechanical corneal trepanation.

Biomolecular markers of malignancy in human uveal melanoma: the role of the cadherin-catenin complex and gene expression profiling.

In recent years there has been a trend towards conservative management of uveal melanoma (UM), aimed at preserving the eye and vision. Despite improvements with this approach, recurrent tumour and metastatic disease still occur, and the management remains problematic. As a result of these limitations, there is interest in gaining a greater understanding of molecular changes associated with aggressive disease patterns in UM. This might result in new, more effective and less toxic therapies as well as provide prognostic information for defining subgroups of patients with a less favourable prognosis as potential candidates for adjuvant therapies. Accumulating evidence over the past decade suggests that disturbance in the cadherin-catenin adhesion complex is critical in the process leading to invasion and metastasis of many cancers. The recent advent of DNA micro-array technology now offers an unprecedented ability to study these molecules and others associated with malignant transformation. In this mini-review, the aspects of tumour progression in which cadherin-catenin may be involved are dealt with along with the potential application of DNA micro-array technology to the problem in UM.