[Selective vital dyes in macular surgery : Do they increase the probability of intraoperative identification of the internal limiting membrane also for an experienced surgeon?] / Selektive Vitalfarbstoffe in der Makulachirurgie : Erhöhen sie die Wahrscheinlichkeit der intraoperativen ILM-Identifizierung auch bei einem erfahrenen Operateur?

BACKGROUND: Various vital dyes exist on the market for intraoperative internal limiting membrane (ILM) identification. The aim of this study was to verify the added value of these dyes for ILM identification and in the difficulty of ILM peeling during pars plana vitrectomy (ppV) by a single surgeon highly experienced in this operation. MATERIAL AND METHODS: In this study 400 ppV surgical reports involving ILM peeling were retrospectively analyzed. Intraoperative assessment of identification or difficulty of intraoperative ILM peeling had to be documented in the surgical report. The total group consisted of 2 cohorts each with 200 surgical reports (first cohort without selective vital dyes, period 2004-2006; second cohort with vital dyes in the majority of ppVs, period 2013-2020). RESULTS: The difference between both groups in terms of intraoperative identification of ILM was statistically significant (p < 0.001); however, no statistically significant difference (p = 0.951) was found between the two groups in terms of difficulty of ILM peeling. In logistic regression analysis neither patient gender, age, eye side, lens status nor posterior vitreous limiting membrane status were significantly associated with ILM identification. CONCLUSION: The introduction of intravital dyes represents a decisive advancement in retinal surgery. In the investigated sample this benefit was evident from two precisely defined surgical cohorts of a single highly experienced surgeon. This underlines the additional benefit of using selective vital dyes to identify ILM in macular surgery for less experienced surgeons.

Current Practice in the Treatment of Epithelial and Melanocytic Tumours with Interferon-α2b: A Survey of Tertiary Eye Centres in Germany.

PURPOSE: To evaluate the standard of care, in particular the use of topical or subconjunctival interferon-α2b, in treating ocular surface squamous neoplasia or melanocytic tumours in tertiary eye centres in Germany. METHODS: A survey containing 14 questions was sent to 43 tertiary eye centres in Germany. The questions addressed the surgical and medical management of ocular surface squamous neoplasia and melanocytic tumours (primary acquired melanosis and malignant melanoma), as well as the clinical experiences and difficulties in prescribing off-label interferon-α2b eye drops and subconjunctival injections. RESULTS: Twenty-four tertiary eye centres responded to the survey. Eighty-three percent of centres had used interferon-α2b in their clinical practice and 25% prescribed it as the first-line cytostatic agent following surgical excision of ocular surface squamous neoplasia, while 10% would do so for melanocytic tumours. Correspondingly, the majority of respondents selected mitomycin C as their first-line agent. Side effects were uncommon with topical interferon-α2b eye drops but were more frequently reported after subconjunctival interferon-α2b injections. In total, eight centres had experience with interferon-α2b injections. The most significant obstacles perceived by ophthalmologists when prescribing interferon-α2b were its high cost and the reimbursement thereof. CONCLUSION: Off-label mitomycin C was the preferred adjuvant therapy for epithelial and melanocytic tumours, with interferon-α2b being the standard second-line option. Interferon-α2b has predominantly been used to treat ocular surface squamous neoplasia and, to a lesser extent, melanocytic tumours at German tertiary eye centres. Following its market withdrawal, supply shortages of interferon-α2b are likely to have a profound impact on patient care and their quality of life.

Incidence, progression and risk factors of age-related macular degeneration in 35-95-year-old individuals from three jointly designed German cohort studies.

OBJECTIVE: To estimate age-related macular degeneration (AMD) incidence/progression across a wide age range. METHODS AND ANALYSIS: AMD at baseline and follow-up (colour fundus imaging, Three Continent AMD Consortium Severity Scale, 3CACSS, clinical classification, CC) was assessed for 1513 individuals aged 35-95 years at baseline from three jointly designed population-based cohorts in Germany: Kooperative Gesundheitsforschung in der Region Augsburg (KORA-Fit, KORA-FF4) and Altersbezogene Untersuchungen zur Gesundheit der Universität Regensburg (AugUR) with 18-year, 14-year or 3-year follow-up, respectively. Baseline assessment included lifestyle, metabolic and genetic markers. We derived cumulative estimates, rates and risk factor association for: (1) incident early AMD, (2) incident late AMD among no AMD at baseline (definition 1), (3) incident late AMD among no/early AMD at baseline (definition 2), (4) progression from early to late AMD. RESULTS: Incidence/progression increased by age, except progression in 70+-year old. We observed 35-55-year-old with 3CACSS-based early AMD who progressed to late AMD. Predominant risk factor for incident late AMD definition 2 was early AMD followed by genetics and smoking. When separating incident late AMD definition 1 from progression (instead of combined as incident late AMD definition 2), estimates help judge an individual's risk based on age and (3CACSS) early AMD status: for example, for a 65-year old, 3-year late AMD risk with no or early AMD is 0.5% or 7%, 3-year early AMD risk is 3%; for an 85-year old, these numbers are 0.5%, 21%, 12%, respectively. For CC-based 'early/intermediate' AMD, incidence was higher, but progression was lower. CONCLUSION: We provide a practical guide for AMD risk for ophthalmology practice and healthcare management and document a late AMD risk for individuals aged <55 years.

Allergic Conjunctivitis: An Update.

Conjunctivitis is a frequent disease of the eye with the typical clinical sign being the "red eye" and comprises a very heterogeneous group with different causes. In general, infectious conjunctivitis must be strictly differentiated from non-infectious conjunctivitis. Allergic conjunctivitis is a subtype of non-infectious conjunctivitis and imposes as an acute, intermittent or chronic, inflammation which is most frequently caused by airborne allergens. The leading clinical sign is chemosis, and patients typically complain about itching. Allergic conjunctivitis is often a reaction to topical and systemic drugs or cosmetics as well as animal hairs from cats and/or dogs. Allergic conjunctivitis is sub-classified into the following forms: seasonal allergic conjunctivitis (also termed: hay fever conjunctivitis), atopic conjunctivitis, vernal conjunctivitis, upper limbal (kerato-) conjunctivitis, and conjunctivitis associated with various oculomucocutaneous syndromes. In each form, there are distinctive features in: clinical appearance, generating agent(s), as well as treatment as listed here.

MuSIC report III: tumour microcirculation patterns and development of metastasis in long-term follow-up of melanocytic uveal tumours.

PURPOSE: To statistically determine differences in microcirculation patterns between nevi and uveal melanomas and the influence of these patterns on metastatic potential in the long-term follow-up of 112 patients with melanocytic uveal tumours. In vivo markers indicating malignancy and metastatic potential have implications for treatment decision. METHODS: Primary diagnosis and work-up included clinical examination, fundus photography, standardized A and B scan echography as well as evaluation of tumour microcirculation patterns via confocal fluorescein and indocyanine green angiography (ICGA). Patient data were collected from the patient files, the tumour registry or personal contact. Statistical analysis was performed with spss 22.0 using chi-square, Fisher's exact test and Kaplan-Meier survival analysis. RESULTS: Forty-three uveal melanocytic lesions remained untreated and were retrospectively classified as benign nevi, whereas 69 lesions were malignant melanomas (T1: 32, T2: 28, T3: 6 and T4: 3). 'Silent' and 'arcs without branching' were found significantly more often in nevi (p = 0.001 and p = 0.010), whereas 'parallel with cross-linking' and 'networks' were significantly more frequent in melanomas (p = 0.022 and p = 0.029). The microcirculation pattern 'parallel with cross-linking' proved significantly more frequent in patients who developed metastases (p = 0.001). CONCLUSIONS: Certain microcirculation patterns may guide us in differentiating uveal nevi from malignant melanomas. A non-invasive prognostic marker can be of great value for borderline lesions in which cytology is less likely taken. 'Parallel with cross-linking' did not only indicate malignancy, but it was also associated with later tumour metastasis.

Osteopontin as a serologic marker for metastatic uveal melanoma: results of a pilot study.

PURPOSE: To evaluate the protein osteopontin (OPN) as a potential new marker for screening and detection of metastatic uveal melanoma. DESIGN: Prospective, clinical study. METHODS: Twenty-eight plasma samples of 27 patients with uveal melanoma were analyzed, and the OPN plasma levels were quantified. Eight of these patients showed liver metastasis. As a control, we measured OPN levels in eight healthy, age-matched individuals. RESULTS: The median plasma concentration of OPN in patients with melanoma without metastasis was 46.78 ng/ml (range, 14.5 to 118.67 ng/ml). In contrast, increased median levels of OPN of 170.72 ng/ml (range, 87.37 to 375.54 ng/ml, P <.001) were seen in eight patients with proven metastatic disease. Healthy patients without uveal melanoma showed a median plasma concentration of OPN of 54.6 ng/ml (range, 38.23 to 71.21 ng/ml). CONCLUSION: The protein OPN seems to be a promising tumor marker for detecting metastatic disease in patients with uveal melanoma.

Indications and clinical outcome of capsular tension ring (CTR) implantation: A review of 9528 cataract surgeries.

BACKGROUND: To report the indications and clinical outcomes of all capsular tension ring (CTR) implantations in a large series of consecutive cataract surgeries during a five year interval in a university eye hospital. METHODS: The study was designed as a restrospective analysis of a consecutive series of 9528 cataract surgeries. The records were checked for cases in which a CTR was implanted. The indications and clinical outcomes of CTR implantation were documented and an evaluation of posterior chamber intraocular lens (PCIOL) insertion, position, and centration. RESULTS: In this series, a CTR was implanted in 69 eyes of 67 patients. The indications were advanced or mature cataract in 40, post-traumatic cataract in 23, pseudoexfoliation syndrome in 4 and subluxated lens in 2 eyes. PCIOL implantation in the capsular bag was possible in 61 (90%) of these 69 eyes. In 5 (7%) additional eyes, PCIOL implantation in the ciliary sulcus was accomplished. In one eye (1%) no IOL implantation was performed because of high myopia. In only two of 69 eyes (2%), an anterior chamber intraocular lens had to be inserted despite prior CTR implantation. In 5 eyes (5%), a slight dislocation of the IOL was noted postoperatively, but none of these patients complained of visually relevant symptoms (eg, monocular diplopia). CONCLUSIONS: According to our experience CTRs are used very infrequently (0.7%), but remain useful in cataract surgeries with difficult preoperative or intraoperative conditions. If zonulolysis is less than two quadrants in extent, implantation of a PCIOL was possible in 98% of cases. Implantation of CTRs with special designs may have additional advantages (eg, inhibition of posterior capsule opacity) and warrant further investigation.

Pulsed electron avalanche knife for capsulotomy in congenital and mature cataract.

The pulsed electron avalanche knife (PEAK-fc, Carl Zeiss Meditec) is an electrosurgical cutting device that allows precise "cold" and traction-free tissue dissection. We describe its applicability and safety for anterior capsulotomy in a child with congenital cataract and an adult patient with mature cataract. The PEAK-fc was set at a voltage of 600 V and a pulse repetition rate of 80 Hz. Anterior capsulotomies were successfully and safely performed in both cases, with the edges of capsulotomies appearing sharp and showing only limited collateral damage. The PEAK-fc appears to be a helpful cutting device for complicated cases of cataract surgery, especially for mature and congenital cataracts.

Pulsed electron avalanche knife in vitreoretinal surgery.

PURPOSE: To evaluate the advantages, disadvantages, safety, and surgical applicability of the pulsed electron avalanche knife (PEAK-fc), a new electrosurgical knife for "cold" and tractionless cutting, in vitreoretinal surgery. PEAK-fc is equipped with an integrated fiberoptic that makes bimanual procedures in intraocular surgery possible. METHODS: A prospective consecutive trial of 18 eyes in 18 patients who underwent vitreoretinal surgery for proliferative diabetic retinopathy, proliferative vitreoretinopathy, subretinal macular hemorrhage, or macular pucker was performed. The following specific maneuvers were performed with PEAK-fc: transection of epiretinal membranes, retinotomies, retinal vessel coagulation, and posterior membranectomy. RESULTS: Detached and attached retina could be dissected successfully in eight cases. Intraoperatively, incision edges were sharply demarcated, showing no visible collateral damage. Deeper layers than the neurosensory retina were not affected. With the bimanual approach, epiretinal avascular and vascular membranes could be removed in 10 cases. Hemorrhages occurring during transection of vascularized membranes could be stopped immediately using the coagulation mode of PEAK-fc. Posterior capsule fibrosis was successfully excised in one patient. No complications were observed. CONCLUSION: PEAK-fc offers precise and tractionless tissue cutting during ocular surgery. Using different waveform parameters, the same device performs cold cutting and/or "hot" coagulation, thus improving the precision, safety, and ergonomics of vitreoretinal surgery.

Trypan blue in macular pucker surgery: an evaluation of histology and functional outcome.

PURPOSE: To evaluate possible adverse effects of trypan blue on the ultrastructure of the human retina, to report on functional outcome of macular pucker surgery with and without the use of trypan blue, and to evaluate the ultrastructure of tissue harvested during surgery. DESIGN: Experimental study and prospective matched-pair analysis of two consecutive, interventional case series. METHODS: Possible adverse effects on the ultrastructure of the human retina by trypan blue were evaluated in three donor eyes in an experimental study using trypan blue in concentrations of 0.02%, 0.15%, and 0.25%. The retinas were histologically evaluated. In the clinical study, the functional outcome (visual acuity, Goldmann perimetry) of 10 eyes of 10 consecutive patients with intraoperative use of trypan blue (0.15%) was analyzed (group 1) and compared with the functional outcome in a matched group of patients (preoperative visual acuity, pre- and postoperative lens status) who had undergone vitrectomy without trypan blue assistance (group 2). Only patients with an idiopathic macular pucker were included. Epiretinal tissue of all eyes was harvested and prepared for ultrastructural analysis using light and electron microscopy. RESULTS: In the postmortem study, no significant alterations of the inner retina suggesting adverse effects of trypan blue concentrations of 0.02% were observed. In contrast, a disorganization of the innermost retina and an absence of the internal limiting membrane (ILM) was seen after the application of undiluted 0.15% and 0.25% trypan blue. In the clinical study, the median best-corrected visual acuity was 20/50 in both groups (range, 20/200-20/40) before surgery. Mean age was 70 years in group 1 (with trypan blue) and 69 years in group 2 (without trypan blue). Mean follow-up time was 4 months in group 1 and 5.6 months in group 2. Postoperatively, median visual acuity had increased to 20/32 (range, 20/100-20/25; Wilcoxon test P = 0.01) in group 1 and to 20/40 (range, 20/100-20/25; P = 0.09) in group 2. The difference between the two groups was not statistically significant (P = 0.4). Four of 10 patients without and 7 of 10 patients with trypan blue staining experienced an improvement of visual acuity (gain of 2 lines or more). No postoperative visual field defects were noted in either group. Histologic analysis of tissue harvested intraoperatively revealed the regular picture of undisturbed fibrocellular membranes. In some specimens, a layer of interspersed collagen was noted between epiretinal cells and the ILM, suggesting two different morphologic types of macular pucker. In a few sections, areas of cellular elements were detected adjacent to the retinal surface of the ILM. CONCLUSION: Trypan blue in a concentration of 0.02% is not associated with morphologic alterations of the inner retinal layers in our postmortem study. After application of 0.15% and 0.25% trypan blue solutions, a disorganization of the inner retinal layers was observed; the ILM was absent. We did not find any adverse effects of an intraocular trypan blue concentration of 0.02% on functional status. Our study further indicates that the functional results of surgery with and without the use of trypan blue are comparable. As the question of toxicity of a dye can not be answered by morphological observations alone, further experimental studies will be needed.

Muscle surgery in patients with Graves' disease using topical anesthesia.

PURPOSE: To report our experience in extraocular muscle surgery for Graves' disease using topical anesthesia. DESIGN: Retrospective, noncomparative, observational case series. PARTICIPANTS: In 135 patients with Graves' disease, a total of 200 ocular muscles were operated during the past 20 years at the Department of Ophthalmology, Ludwig-Maximilian-University, Munich, Germany. METHODS: Surgery was performed under topical anesthesia with tetracaine hydrochloride 1% eyedrops. Because of the restrictive nature of the motility impairment, recession of the muscles was used in all patients. The exact amount of recession was determined during the operation with active cooperation from the patient. MAIN OUTCOME MEASURES: Binocular single vision and the angle of deviation were evaluated preoperatively and postoperatively. RESULTS: Postoperative binocular single vision in the primary position was achieved by 78.7% of the patients on the first postoperative day. Subsequent evaluation demonstrated binocular single vision in 91.9% of all patients and in 96.4% of the group with only 1 muscle (inferior rectus) operated. CONCLUSIONS: The authors have demonstrated that topical anesthesia is a feasible and reliable method for performing extraocular muscle surgery in patients with Graves' disease. Intraoperative patient discomfort seemed insignificant, and the active cooperation of the patient in finding the appropriate extent of surgery was advantageous. The overall results showed that deviation surgery with the use of topical anesthesia is highly successful in restoring binocular single vision in patients with endocrine orbitopathy.

Functional outcome after trypan blue-assisted vitrectomy for macular pucker: a prospective, randomized, comparative trial.

PURPOSE: To evaluate functional outcome after the intraoperative application of 0.06% trypan blue during vitrectomy for macular pucker. DESIGN: Prospective, randomized, comparative study. METHODS: Forty-three eyes of 43 consecutive patients, 30 women and 13 men, were incorporated in the study. Patients were randomized into two groups: group 1 (n = 22) with trypan blue (0.06%) staining, and group 2 (n = 21) without trypan blue staining. Functional outcome (best-corrected visual acuity, Goldmann perimetry) was evaluated 1 day before surgery, at 6 weeks, and at intervals of 3, 6, and 12 or more months postoperatively. Only patients with an idiopathic macular pucker were included. In all patients, a standard three-port pars plana vitrectomy with peeling of an epiretinal membrane (ERM) and the internal limiting membrane was performed. No other modification of the surgical procedure, except the use of trypan blue was made between the two groups. RESULTS: Mean age was 68.9 years in group 1 (with trypan blue) and 69.4 in group 2 (without trypan blue). Median best-corrected visual acuity was 20/63 in both groups (range, 20/200-20/40; P >.5) before surgery. Mean follow-up time was 5.8 months in group 1 and 5.3 months in group 2. After surgery, median visual acuity had increased to 20/40 in both groups (range, 20/500 to 20/20 in group 1 and 20/100 to 20/20 in group 2; P <.001 for both groups). The difference between both groups was not statistically significant (P >.5). An improvement of visual acuity (gain of 2 or more lines) was seen in 16 patients of both groups. No postoperative visual field defects were noted. CONCLUSIONS: Trypan blue-assisted vitrectomy for macular pucker leads to good functional results with no dye-related adverse effects after short follow-up. Trypan blue might be especially applicable in cases in which the borders of the ERM are difficult to define. Hypothetical advantages, such as fewer recurrences of ERMs after trypan blue staining, will have to be evaluated during further follow-up of patients.

Evaluation of minimally invasive therapies and rationale for a prospective randomized trial to evaluate selective intra-arterial lysis for clinically complete central retinal artery occlusion.

OBJECTIVES: To determine the effect of commonly used minimally invasive treatments for clinically complete nonarteritic central retinal artery occlusion (CRAO) and design a prospective randomized trial to evaluate selective intra-arterial lysis for this condition. METHODS: In this retrospective noncomparative case series, all medical records of patients with a diagnosis of CRAO treated at the Department of Ophthalmology, Ludwig-Maximilians-Universität, Munich, Germany, from 1994 through 1999 were reviewed for treatments administered and course of visual acuity. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA) at initial and last visit. RESULTS: We identified 102 patient medical records; 71 were suitable for further analysis. Forty-four (62%) of the 71 patients included were treated with oral acetylsalicylate; 44 (62%), with oral acetazolamide; 32 (45%), with ocular massage; 22 (31%), with isovolemic hemodilution; 19 (27%), with oral pentoxifylline; 8 (11%), with topical beta-blocker; 6 (8%), with paracentesis of the anterior chamber; 4 (6%), with subcutaneous heparin. A mean +/- SD number of treatments of 2.5 +/- 1.4 was administered per patient, and BCVA increased by a mean +/- SD number of Snellen lines of 0.7 +/- 2.8. The BCVA in 11 patients (15%) increased by 3 or more lines. Multivariate stepwise regression did not reveal any single or combination treatment as a significant factor for improvement in BCVA. Patient age and duration of visual impairment before initial examination were not significant predictors of final BCVA. CONCLUSIONS: Commonly used minimally invasive treatments of CRAO do not improve the natural course of the disease. A prospective trial by the European Assessment Group for Lysis in the Eye is under way to evaluate selective intra-arterial lysis, and in this trial some of these minimally invasive treatments are used in the control group.

Optical coherence tomography for the detection of laser in situ keratomileusis in donor corneas.

PURPOSE: In 2001, more than one million laser in situ keratomileusis (LASIK) procedures were performed worldwide. Considering the increasing number of refractive procedures, eye banks will be increasingly confronted with the problem of how to identify those donors with prior refractive surgery. To date, efficient screening methods to identify LASIK surgery in donor eyes have not been established. Therefore, the purpose of the current study was to determine whether optical coherence tomography (OCT) can be used to detect the presence of LASIK-induced changes in human corneas. METHODS: Laser in situ keratomileusis was performed on 20 organ-cultured human cornea disks. The excimer laser ablation performed ranged from 0 to 12 diopters. The corneas were maintained in culture, and the visibility of flap-stromal interface by OCT was assessed up to 6 months after the LASIK procedure. Additionally, two donor corneas with the history of LASIK treatment before death were screened for structural changes. RESULTS: Optical coherence tomography scans were able to detect the interface between the corneal flap and the residual stromal tissue in all corneas and at all examined time intervals. There were no differences in signal intensity among the different depths of ablation. The relative signal intensity of the interface compared with the averaged stromal intensity ranged from 2.1 to 6.0. In both donor corneas with suspected prior LASIK surgery, OCT scanning showed the characteristic stromal interface as found in the in vitro model. CONCLUSIONS: Corneal examination by OCT could be an appropriate technique for eye banks to screen donor corneas for prior LASIK surgery.

Complex microcirculation patterns detected by confocal indocyanine green angiography predict time to growth of small choroidal melanocytic tumors: MuSIC Report II.

PURPOSE: Multiple independent laboratories have confirmed the histologic observation that some tumor microcirculation patterns (MCPs) in uveal melanomas are associated strongly with death resulting from metastatic disease. Because these patterns are imageable with confocal indocyanine green angiography (ICG), we designed a prospective study to evaluate whether these angiographically detectable MCPs predict time to tumor growth. DESIGN: Observational case series, prospective, non-randomized. PARTICIPANTS: Ninety-eight patients with unilateral, small, choroidal melanocytic tumors. METHODS: The following information and tumor characteristics were recorded for each patient: demographic parameters, best-corrected visual acuity, intraocular pressure, related visual symptoms, location and dimension of tumor, pigmentation, orange pigment, drusen, tumor-associated hemorrhage, subretinal fluid, and confocal ICG angiographically determined microcirculation patterns-silent (avascularity), normal (preexisting normal choroidal vessels within the tumor), straight vessels, parallel without and with cross-linking, arcs without and with branching, loops, and networks. MAIN OUTCOME MEASURES: Time to growth of the tumor, with growth defined as an increase in the maximal apical tumor height of 0.5 mm measured by standardized A-scan ultrasonography, photographic documentation of an increase of the largest basal diameter of at least 1.5 mm, advancement of one tumor border of at least 0.75 mm, or a combination thereof. RESULTS: Twenty-eight of the 98 tumors in this study (29%) met the predetermined criteria for tumor growth. The median time to growth was 127 days (range, 51-625 days). The following tumor characteristics were significantly associated with time to tumor growth: flashes (P = 0.0224), orange pigment (P = 0.012), subretinal fluid (P < 0.001), maximum basal tumor diameter at initial examination (P = 0.015), maximum apical tumor height (P < 0.001), parallel with cross-linking MCP (P < 0.001), arcs with branching MCP (P = 0.006), loops (P < 0.001), and networks (P < 0.001). Of these, the angiographic documentation of any of the complex MCPs (parallel with cross-linking, arcs with branching, loops, networks, or a combination thereof) showed the strongest association with the time to tumor growth in a Cox proportional hazard model. CONCLUSIONS: The characteristics of our patient cohort are comparable by clinical and echographic parameters with cohorts for predicting tumor growth, described previously in the literature. In addition, we detected a novel clinical predictor of tumor growth: the confocal ICG angiographic detection of complex MCPs.

An orthotopic model for human uveal melanoma in SCID mice.

The microcirculation of primary uveal melanomas, their precursors, and their metastases is distinctive. Medium-sized and even large primary uveal melanomas typically lack significant zones of necrosis, suggesting that either these tumors are relatively well perfused or they are capable of growth in a severely blood-deprived microenvironment. In addition to normal choroidal vessels that are incorporated into nevi and most primary uveal melanomas, aggressive primary and metastatic uveal melanomas tend to contain patterns of extracellular matrix that surround spheroidal or cylindrical packets of tumor cells. Some components of this branching, looping, and interconnected system of matrix may be perfused. It is now known that the generation of this patterning is a characteristic of genetically dysregulated melanoma cells (nonaggressive tumor cells do not form these patterns and melanomas lacking branching, looping, or interconnected matrix patterns tend to follow a relatively indolent course). We developed an orthotopic model of an aggressive human uveal melanoma by injecting suspensions of the primary human choroidal melanoma cell line (OCM1) into the subretinal space of one eye of 20 SCID mice. All mice were examined daily for tumor growth and tumors developed in every eye within 3 weeks of injection. The tumors were characterized by extraocular extension and the development of looping matrix patterns characteristic of those seen in aggressive human uveal melanoma. As in human uveal melanomas, these patterns were perfused by blood in areas. The orthotopic injection of human uveal melanoma cells into the SCID mouse eye generates a model reproducing the matrix-associated microcirculatory patterns of aggressive primary human uveal melanomas. This model can be used to explore the molecular pathogenesis and modulation of this novel circulation in vivo, to facilitate our understanding of the blood flow to these tumors providing insight into perfusion and drug delivery, to enable testing of pharmacologic modulation of pattern formation and intratumoral blood flow, and to refine noninvasive methods such as confocal scanning laser ophthalmoscopy to detect the presence of these patterns by which ophthalmologists might assess the biological behavior of tumors as noninvasive substitute for biopsy.

The effect of prinomastat (AG3340), a synthetic inhibitor of matrix metalloproteinases, on uveal melanoma rabbit model.

PURPOSE: We studied the effects of intravitreally administered prinomastat on the take rate and growth of uveal melanoma after xenograft implantation in rabbit uveal melanoma model. METHODS: Uveal melanoma xenograft was implanted to suprachoroidal space in each eye of 24 pigmented rabbits which were immunosuppressed with cyclosporine. One week after surgery, the eyes were randomized to receive prinomastat or the vehicle of the prinomastat intravitreally every week for 4 weeks. The take rate of the xenograft, tumor height, apoptosis, and necrosis in the eyes which developed tumors from the treatment and control groups were compared. RESULTS: A tumor mass was identified in 8 of 24 (33%) prinomastat-treated eyes and 20 of 24 (83%) of the vehicle-treated eyes. Echographic measurements revealed a mean tumor height of 2.2 mm in the prinomastat-treated group and 3.8 mm in the control group in those eyes with take of tumor (p < 0.001). Stereomicroscopic measurements showed a mean tumor height of 1.9 mm in the treatment group and 3.9 mm in the control group (p < 0.001). The mean number of apoptotic nuclei detected per mm(2) of the histologic section in the non-necrotic tumor was 8.12 in the prinomastat-treated group and 0.57 in the control group (p < 0.001). Evaluation of the digital images in microscopic sections of the tumors on histologic slides revealed 29.6% necrosis in prinomastat-treated eyes as compared to 10.9% in vehicle-treated eyes (p = 0.003). CONCLUSIONS: These results suggest that prinomastat treatment significantly reduces the take rate and the growth rate of xenograft in uveal melanoma rabbit model.

Transpupillary thermotherapy (TTT) in circumscribed choroidal hemangioma.

BACKGROUND: Choroidal hemangioma presents a therapeutic dilemma. Although it is a benign tumor, it may lead to massive exudation of subretinal fluid and a loss of visual function. Argon laser photo-coagulation in a grid pattern may be followed by initial absorption of subretinal fluid, but recurrence is common. Trans-scleral cryotherapy is difficult to apply at the posterior pole of the eye. External beam irradiation may bear a risk of maculopathy and papillopathy. Brachytherapy does not allow placement of radiation to the hemangioma sparing other retinal or choroidal structures. We sought to determine whether transpupillary thermotherapy (TTT) is suitable for treatment of choroidal hemangioma at the posterior pole. METHODS: We present ten patients with choroidal hemangioma. All of these received TTT. The mean follow-up period was 13.3 months (3-21 months). TTT was delivered via a slitlamp microscope with a diode laser at 810 nm. RESULTS: After TTT, reduction in tumor prominence was observed in eight patients at 3 months after treatment by A scan sonography. Visual acuity improved by more than three lines in four patients, and remained unchanged in all other patients. Two patients were retreated to achieve complete absorption of fluid. Serous retinal detachment persisted in three patients because the hemangioma could not be treated completely because of proximity to the fovea. CONCLUSION: Our preliminary results suggest that TTT may be used effectively to treat some choroidal hemangiomas in the first instance and prevent fluid leakage provided the lesion does not involve the fovea. However, long-term follow-up and more cases are needed to evaluate the long-term visual outcome and potential risks.