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To revisit the independent importance of ciliary body involvement (CBI), monosomy 3 (M3), tumour size, histological and clinical factors in uveal melanoma (UM) and to devise a new prognostic classification based on a combination of the American Joint Committee on Cancer (AJCC) and the Cancer Genome Atlas (TCGA) models.Two cohorts with a total of 1796 patients were included. Clinicopathological factors were compared between patients with and without CBI and M3. Development of the prognostic classification was performed in a training cohort and was then tested in two independent validation cohorts.Tumours with CBI were more common in women, had greater apical thickness, greater basal tumour diameter, greater rates of vasculogenic mimicry and greater rates of M3, were more often asymptomatic at diagnosis and had poorer 5- and 10-year globe conservation rates (p 0.023). In multivariate logistic regression, patient age at diagnosis, tumour diameter and CBI were independent predictors of M3 (p 0.001). In multivariate Cox regression, male sex, age at diagnosis, tumour diameter, M3 and CBI were independent predictors of metastasis. The proposed prognostic classification combined patient age, sex, CBI, extraocular extension, M3, 8q (optional) and tumour size, and demonstrated greater prognostic acumen than both AJCC 4 T categories and TCGA groups A to D in validation cohorts.Tumour size does not confound the prognostic implication of CBI, M3, male sex and age at diagnosis in UM. These factors were included in a new prognostic classification that outperforms AJCC T category and TCGA groups.

PurposeTo develop a prognostic test based on serum samples obtained at diagnosis of uveal melanoma (UM).DesignRetrospective cohort study.SubjectsEighty-three patients diagnosed with primary melanoma in the choroid or ciliary body at St. Erik Eye Hospital, Stockholm, Sweden between 1996 and 2000. Serum samples from peripheral blood were obtained at diagnosis and kept at -80 °C until this analysis.MethodsProteome profiling of 84 different cancer-related proteins was used to screen for potential biomarkers. ELISA was then performed to evaluate the serum levels of the best candidates. Receiver operating characteristics were used to define thresholds for metastatic risk. A prognostic test that stratifies patients into low, intermediate, and high metastatic risk categories was developed (serUM-Px) in a training cohort and tested in a validation cohort.ResultsOf the 83 included patients, 43 (52 %) were female. The mean tumor diameter and thickness was 9.8 mm (SD 3.7) and 4.9 mm (SD 2.3), respectively. Twenty-two patients succumbed to metastatic UM and forty-two patients died from other causes. The median follow-up for the 19 survivors was 22.7 years (IQR 22.3-23.0). In proteome profiling, five proteins (Leptin, Osteopontin, Progranulin, Tenascin C and DLL1) were included for further analysis. After ELISA of individual proteins, Leptin and Osteopontin were selected for inclusion in the serUM-Px prognostic test. The test was developed in a training cohort (n=17) and then validated in an independent cohort (n=62). Patients had gradually shorter metastasis-free survival and greater incidence of UM-related mortality in competing risk analysis with increasing metastatic risk category (p = 0.02 and 0.027, respectively). In multivariate Cox regression, serUM-Px was an independent predictor of metastasis with tumor diameter, tumor thickness and patient age at diagnosis as covariates (hazard ratio 2.4, 95 % CI 1.0 to 5.3).ConclusionsserUM-Px, a prognostic test based on a single peripheral venous blood sample at the time of UM diagnosis, stratifies patients into low, intermediate and high metastatic risk categories. It predicts metastases many years in advance in a validation cohort with very long follow-up. Future studies should aim to confirm these findings prospectively.

As the p53 tumor suppressor is rarely mutated in conjunctival melanoma (CM), we investigated its activation as a potential therapeutic strategy. Preventing p53/Mdm2 interaction by Nutlin-3, the prototypical Mdm2 antagonist, or via direct siRNA Mdm2 depletion, increased p53 and inhibited viability in CM cell lines. The sensitivity to Nutlin-3 p53 reactivation with concomitant Mdm2 stabilization was higher than that achieved by siRNA, indicative of effects on alternative Mdm2 targets, identified as the cancer-protective IGF-1R. Nutlin-3 treatment increased the association between IGF-1R and β-arrestin1, the adaptor protein that brings Mdm2 to the IGF-1R, initiating receptor degradation in a ligand-dependent manner. Controlled expression of β-arrestin1 augmented inhibitory Nutlin-3 effects on CM survival through enhanced IGF-1R degradation. Yet, the effect of IGF-1R downregulation on cell proliferation is balanced by β-arrestin1-induced p53 inhibition. As mitomycin (MMC) is a well-established adjuvant treatment for CM, and it triggers p53 activation through genotoxic stress, we evaluated how these alternative p53-targeting strategies alter the cancer-relevant bioactivities of CM. In 2D and 3D in vitro models, Nutlin-3 or MMC alone, or in combination, reduces the overall cell tumor growth ~30%, with double treatment inhibition rate only marginally higher than single-drug regimens. However, histopathological evaluation of the 3D models revealed that Nutlin-3 was the most effective, causing necrotic areas inside spheroids and complete loss of nuclear staining for the proliferative marker Ki67. These findings were further validated in vivo; zebrafish xenografts demonstrate that Nutlin-3 alone has higher efficacy in restraining CM tumor cell growth and preventing metastasis. Combined, these results reveal that β-arrestin1 directs Mdm2 toward different substrates, thus balancing IGF-1R pro-tumorigenic and p53-tumor suppressive signals. This study defines a potent dual-hit strategy: simultaneous control of a tumor-promoter (IGF-1R) and tumor-suppressor (p53), which ultimately mitigates recurrent and metastatic potential, thus opening up targeted therapy to CM.

ObjectiveTo analyse ocular and systemic findings of patients presenting with systemic metastasis.Methods and analysisIt is an international, multicentre, internet-enabled, registry-based retrospective data analysis. Patients were diagnosed between 2001 and 2011. Data included: primary tumour dimensions, extrascleral extension, ciliary body involvement, American Joint Committee on Cancer (AJCC)-tumour, node, metastasis staging, characteristics of metastases.ResultsOf 3610 patients with uveal melanoma, 69 (1.9%; 95% CI 1.5 to 2.4) presented with clinical metastasis (stage IV). These melanomas originated in the iris, ciliary body and choroid in 4%, 16% and 80% of eyes, respectively. Using eighth edition AJCC, 8 (11%), 20 (29%), 24 (35%), and 17 (25%) belonged to AJCC T-categories T1–T4. Risk of synchronous metastases increased from 0.7% (T1) to 1.5% (T2), 2.6% (T3) and 7.9% (T4). Regional lymph node metastases (N1a) were detected in 9 (13%) patients of whom 6 (67%) had extrascleral extension. Stage of systemic metastases (known for 40 (59%) stage IV patients) revealed 14 (35%), 25 (63%) and 1 (2%) had small (M1a), medium-sized (M1b) and large-sized (M1c) metastases, respectively. Location of metastases in stage IV patients were liver (91%), lung (16%), bone (9%), brain (6%), subcutaneous tissue (4%) and others (5%). Multiple sites of metastases were noted in 24%. Compared with the 98.1% of patients who did not present with metastases, those with synchronous metastases had larger intraocular tumours, more frequent extrascleral extension, ciliary body involvement and thus a higher AJCC T-category.ConclusionsThough higher AJCC T-stage was associated with risk for metastases at diagnosis, even small T1 tumours were stage IV at initial presentation. The liver was the most common site of metastases; however, frequent multiorgan involvement supports initial whole-body staging.

BackgroundEpiscleral brachytherapy is the most common eye-preserving treatment for medium-sized choroidal melanomas. γ-emitting iodine-125 (125I) and β-emitting ruthenium-106 (106Ru) are widely used. The latter is however generally reserved for thinner tumours (MethodsAll patients with ≥5.5 mm thick choroidal melanomas who were treated with plaque brachytherapy at a single institution between 1 November 1979 and 31 December 2015 were included (n=571). Size-controlled Cox regression HRs for postbrachytherapy enucleation, repeated brachytherapy and melanoma-related mortality were calculated, as well as Kaplan-Meier disease-specific survival and relative 10-year survival in matched subgroups.Results317 patients were treated with 106Ru and 254 with 125I. The rate of repeated brachytherapy was significantly higher among patients treated with 106Ru (8%) than with 125I (1%, p125I vs 106Ru 0.7, p=0.083) and melanoma-related mortality were not significant (125I vs 106Ru 1.1, p=0.63). Similarly, Kaplan-Meier disease-specific and relative 10-year survival was comparable in matched groups of 5.5–7.4 mm (relative survival 106Ru 59%, 125I 56%) and ≥7.5 mm thick tumours (relative survival 106Ru 46%, 125I 44%).ConclusionsRates of repeated brachytherapy were significantly higher among patients treated with 106Ru versus 125I for thick choroidal melanomas. There were, however, no significant differences in rates of enucleation or patient survival.

BackgroundThe travel distance from home to a treatment centre, which may impact the stage at diagnosis, has not been investigated for retinoblastoma, the most common childhood eye cancer. We aimed to investigate the travel burden and its impact on clinical presentation in a large sample of patients with retinoblastoma from Africa and Europe.MethodsA cross-sectional analysis including 518 treatment-naïve patients with retinoblastoma residing in 40 European countries and 1024 treatment-naïve patients with retinoblastoma residing in 43 African countries.ResultsCapture rate was 42.2% of expected patients from Africa and 108.8% from Europe. African patients were older (95% CI −12.4 to −5.4, pConclusionsFewer than half the expected number of patients with retinoblastoma presented to African referral centres in 2017, suggesting poor awareness or other barriers to access. Despite the relatively shorter distance travelled by African patients, they presented with later-stage disease. Health education about retinoblastoma is needed for carers and health workers in Africa in order to increase capture rate and promote early referral.

A 66-year-old man with castration-resistant prostate cancer was evaluated with F-prostate-specific membrane antigen (PSMA) 1007 PET/CT, which revealed extensive PSMA-positive skeletal metastases in the skull, thorax, spine, pelvis, and extremities. He was then treated Lu-PSMA-617 therapy. Twenty-four-hour SPECT/CT revealed additional activity not seen with F-PSMA adjacent to his left eye. The lesion was biopsied after the first cycle due to pain. This activity was not visible on SPECT/CT after the second treatment cycle, and his eye pain has resolved.

BackgroundEpiscleral brachytherapy is the most common treatment for medium-sized choroidal melanomas. Although controversial, inadequate brachytherapy dose and dose rates have at least a hypothetical implication on patient survival.MethodsAll patients who received ruthenium-106 or iodine-125 brachytherapy for choroidal melanoma at St. Erik Eye Hospital 1996 to 2016 were included (n=1238). Cox regression hazard ratios for melanoma-related mortality across deciles, quartiles and individual integers of apex radiation doses (Gy) and dose rates (Gy/hour) were calculated, adjusted for tumour size and location.ResultsThe average radiation dose at the tumour apex ranged from 73.0 Gy in the first decile to 108.6 Gy in the tenth. Decreasing apex dose by 1 Gy increments or by decile or quartile group was not associated with melanoma-related mortality (p>0.2) The average radiation dose rate at the tumour apex ranged from 0.5 Gy/hour in the first decile to 2.8 Gy/hour in the tenth. Similarly, decreasing apex dose rate by 1 Gy/hour increments or by decile or quartile groups was not associated with melanoma-related mortality (p>0.5).ConclusionThere are no increased hazards for choroidal melanoma-related mortality after brachytherapy with decreasing doses between 108.6 and 73.0 Gy, or with decreasing dose rates between 2.8 and 0.5 Gy/hour.

Uveal melanoma is the most common primary intraocular malignancy in adults, with nearly half of all patients eventually developing metastases, which are invariably fatal. Manual assessment of the level of expression of the tumor suppressor BRCA1-associated protein 1 (BAP1) in tumor cell nuclei can identify patients with a high risk of developing metastases, but may suffer from poor reproducibility. In this study, we verified whether artificial intelligence could predict manual assessments of BAP1 expression in 47 enucleated eyes with uveal melanoma, collected from one European and one American referral center. Digitally scanned pathology slides were divided into 8176 patches, each with a size of 256 &times, 256 pixels. These were in turn divided into a training cohort of 6800 patches and a validation cohort of 1376 patches. A densely-connected classification network based on deep learning was then applied to each patch. This achieved a sensitivity of 97.1%, a specificity of 98.1%, an overall diagnostic accuracy of 97.1%, and an F1-score of 97.8% for the prediction of BAP1 expression in individual high resolution patches, and slightly less with lower resolution. The area under the receiver operating characteristic (ROC) curves of the deep learning model achieved an average of 0.99. On a full tumor level, our network classified all 47 tumors identically with an ophthalmic pathologist. We conclude that this deep learning model provides an accurate and reproducible method for the prediction of BAP1 expression in uveal melanoma.

Purpose To collect comprehensive data on choroidal and ciliary body melanoma (CCBM) in children and to validate hypotheses regarding pediatric CCBM: children younger than 18 years, males, and those without ciliary body involvement (CBI) have more favorable survival prognosis than young adults 18 to 24 years of age, females, and those with CBI. Design Retrospective, multicenter observational study. Participants Two hundred ninety-nine patients from 24 ocular oncology centers, of whom 114 were children (median age, 15.1 years; range, 2.7–17.9 years) and 185 were young adults. Methods Data were entered through a secure website and were reviewed centrally. Survival was analyzed using Kaplan-Meier analysis and Cox proportional hazards regression. Main Outcome Measures Proportion of females, tumor-node-metastasis (TNM) stage, cell type, and melanoma-related mortality. Results Cumulative frequency of having CCBM diagnosed increased steadily by 0.8% per year of age between 5 and 10 years of age and, after a 6-year transition period, by 8.8% per year from age 17 years onward. Of children and young adults, 57% and 63% were female, respectively, which exceeded the expected 51% among young adults. Cell type, known for 35% of tumors, and TNM stage (I in 22% and 21%, II in 49% and 52%, III in 30% and 28%, respectively) were comparable for children and young adults. Melanoma-related survival was 97% and 90% at 5 years and 92% and 80% at 10 years for children compared with young adults, respectively ( P = 0.013). Males tended to have a more favorable survival than females among children (100% vs. 85% at 10 years; P = 0.058). Increasing TNM stage was associated with poorer survival (stages I, II, and III: 100% vs. 86% vs. 76%, respectively; P = 0.0011). By multivariate analysis, being a young adult (adjusted hazard rate [HR], 2.57), a higher TNM stage (HR, 2.88 and 8.38 for stages II and III, respectively), and female gender (HR, 2.38) independently predicted less favorable survival. Ciliary body involvement and cell type were not associated with survival. Conclusions This study confirms that children with CCBM have a more favorable survival than young adults 18 to 25 years of age, adjusting for TNM stage and gender. The association between gender and survival varies between age groups.

Background: In several malignancies, gender-based survival differences after specific therapeutic interventions have been demonstrated. It is not known whether such differences exist after plaque brachytherapy of uveal melanoma. Methods: All patients who received brachytherapy for uveal melanoma at St. Erik Eye Hospital from November 1, 1979 through November 20, 2017 were included (n = 1,541). Retrospective data were retrieved including baseline patient and tumor characteristics, brachytherapy nuclide (ruthenium-106 or iodine-125), radiation dose, treatment duration, tumor relapses, date of metastasis, and cause of death. Results: A total of 775 men and 766 women were treated with plaque brachytherapy. There were no significant differences between the genders in baseline characteristics, treatment, or follow-up. Men and women had similar rates of tumor relapses, hazard for repeated brachytherapy (men vs. women 0.8, p = 0.47), enucleation-free survival, and survival after detection of metastasis. Five-, 10-, and 15-year melanoma-related mortality was 14, 24, and 27% for men and 15, 26, and 32% for women, respectively. There were no significant differences in hazard for melanoma-related mortality (men vs. women 0.9, p = 0.32), median Kaplan-Meier disease-specific survival (men 18.2 years, women 15.5 years, p = 0.22), or median overall survival (men 13.5 years, women 12.6 years, p = 0.60). Conclusion: There are no relevant differences between men and women in ocular or patient survival after brachytherapy for uveal melanoma.

In 1930, Sir Foster Moore first used brachytherapy for uveal melanoma by inserting radon-222 seeds directly into the tumor (Moore, Br J Ophthalmol 14:145–152, 1930). This technique was later modified by Stallard and eventually further refined using radioactive plaques containing cobalt-60 anchored to the episcleral surface (Stallard, Br J Ophthalmol 32(9):618–639, 1948; Stallard, Br J Ophthalmol 50(3):147–155, 1966). In the United States, this radionuclide was gradually replaced by plaques loaded with iodine-125 seeds, as this provided less radiation to surrounding tissues (Sealy et al., Br J Radiol 49(582):551–554, 1976; Packer and Rotman, Ophthalmology 87(6):582–590, 1980). In Europe, the pioneering work of Lommatzsch in the 1970s led to the introduction of ruthenium-106 as a radioactive source for episcleral brachytherapy of uveal melanoma (Lommatzsch, Surv Ophthalmol 19(2):85–100, 1974). Although observational data suggested that there was no survival difference compared to patients enucleated for uveal melanoma, it had not been confirmed in a randomized control trial until the Collaborative Ocular Melanoma Study (COMS) was launched in the mid-1980s. This included patients with medium-sized uveal melanoma, who had equal 5-year and 10-year survival rates in the enucleation and iodine brachytherapy groups (Collaborative Ocular Melanoma Study Group, Arch Ophthalmol 119:969–982, 2001; Collaborative Ocular Melanoma Study Group, Arch Ophthalmol 124:1684–1693, 2006). Ever since, brachytherapy has been a mainstay treatment within this size group. Smaller tumors are generally observed for growth or in selected cases treated with transpupillary thermotherapy, while patients with larger tumors still undergo enucleation.

Purpose Reduced nuclear expression of BRCA1 associated protein 1 (BAP-1) is associated with a high risk for metastasis in uveal melanoma. Manual assessment of the expression level may face issues with interobserver reproducibility. This could be improved with digital image analysis (DIA). Methods Thirty enucleated eyes with uveal melanoma from the Emory Eye Center (Atlanta, GA; years 2009-2017) were included and stained with BAP-1. Retrospective data on patient and tumor characteristics were retrieved. Patients were randomized to a training or validation cohort. Their tumor sections were digitally scanned and scored for percentage of BAP-1-positive cells with the QuPath Bioimage analysis software. Results Interobserver concordance was 75% (Cohen's κ 0.52) with manual BAP-1 scoring and 88% to 94% with DIA (Cohen's κ 0.75-0.88). Positive and negative predictive values for metastasis were 90% and 100% with DIA, 80% and 86% with manual scoring, and 78% and 88% with gene expression class 2. In binary logistic regression, manual and DIA of BAP-1 and gene expression class 2 were associated with metastasis, but none retained significance in multiple regression. Metastasis-free survival was significantly shorter with low BAP-1 expression as defined by DIA (log-rank P = 0.02), but not with manual scoring (log-rank P = 0.36) or with gene expression class 2 (log-rank P = 0.17). Conclusions DIA of BAP-1 is a competitive alternative to manual assessment as well as gene expression profiling in prognostication of enucleated specimens with uveal melanoma. Translational relevance The emerging scope for automatization of qualified diagnostic tasks is applied to uveal melanoma.

Purpose The aim of this study was to compare conventional and novel size estimation methods' ability to predict survival in uveal melanoma (UM). Methods The study was designed as a retrospective consecutive chart review of patients with UM, enucleated between the years 1984 and 1993. Area and volume were estimated based on the largest histopathological cross-section, the second centroid theorem of Pappus and digital image analysis, correlated to overall and relative survival. Results Of 168 patients analysed, 20 (12%) of tumours were categorized as T1, 47 (28%) as T2, 67 (40%) as T3 and 19 (11%) as T4 (15 N/a). A total of 91 tumours with complete survival and measurement data were included and recategorized into small, medium and large volume groups. Increased separation of overall survival was seen compared with current American Joint Committee on Cancer T categories. Difference between the large and small volume groups was 8.6 years (p = 0.001), compared to a difference of 5.6 years (p = 0.091) between T1 and T4. Hazard ratio for all-cause mortality in the large versus small volume group was 2.6 compared to 1.9 for T4 versus T1. Relative survival rates for small, medium and large volumes were 62, 44 and 31% at 10 years, versus 50, 45, 56 and 0% for T1, T2, T3 and T4. Conclusion This study provides evidence that a novel UM volume estimation method might offer a practical and cost-efficient alternative to improve the prognostic value intrinsic to a tumour's size.

To evaluate the efficacy of intraocular injections with bevacizumab over 12 months in patients with macular edema (ME) secondary to central retinal vein occlusion (CRVO).A prospective study including a randomized 6-month, sham injection-controlled, double-masked clinical trial followed by a 6-month open-label extension.Sixty patients with ME secondary to CRVO.At baseline, patients were randomized 1:1 to receive intraocular injections of bevacizumab or sham injections every 6 weeks for 6 months. From month 6, all patients received intraocular injections of bevacizumab every 6 weeks for 6 months.The primary outcome measure was the proportion of patients gaining at least 15 letters at 12 months. Secondary outcome measures included mean change from baseline best-corrected visual acuity (BCVA), change in foveal thickness, and development of neovascular glaucoma.At the end of follow-up, 18 of 30 patients (60.0%) in the bevacizumab/bevacizumab (bz/bz) group had gained ≥ 15 letters compared with 10 of 30 patients (33.3%) in the sham/bevacizumab (sh/bz) group (P0.05). The BCVA improved by 16.0 letters at 12 months in the bz/bz group compared with 4.6 letters in the sh/bz group (P0.05). In an unplanned retrospective analysis, patients aged70 years had a significantly worse outcome when receiving delayed treatment, losing 1.4 letters (95% confidence interval [CI], -9.7 to 8.4) in the sh/bz group compared with a gain of 20.1 letters (95% CI, 13.9-26.3) in the bz/bz group in patients aged70 years (P0.003). The mean decrease in central retinal thickness (CRT) was 435 μm in the bz/bz group compared with 404 μm in the sh/bz group (P = not significant). No patients developed iris rubeosis during the 6-month open-label extension period. There were no events of endophthalmitis, retinal tear, or retinal detachment during the 12-month treatment period. No serious nonocular adverse events were reported.Intraocular injections of bevacizumab given every 6 weeks for 12 months improve visual acuity (VA) and reduce ME significantly. Patients receiving delayed treatment have a limited visual improvement.Proprietary or commercial disclosure may be found after the references.

To compare the effect of combined low-dose transpupillary thermotherapy (TTT) and intravitreal ranibizumab with sham TTT and intravitreal ranibizumab in patients with neovascular age-related macular degeneration (AMD).A 24-month, double-masked, randomised, active-controlled clinical trial. 100 patients with primary neovascular AMD were randomly assigned (1:1) to receive intravitreal ranibizumab and sham TTT or intravitreal ranibizumab and low-dose TTT. After an initial loading phase of ranibizumab patients were assigned to receive quarterly low-dose TTT (136 mW/mm) or sham TTT for 24 months. Retreatment with ranibizumab was allowed in both treatment groups using a variable dosing regimen. The primary endpoint was the number of intravitreal injections with ranibizumab. Secondary endpoints included change in best corrected visual acuity (BCVA), central retinal thickness (CRT) and lesion area.In the per protocol (PP) population (78 patients) the mean number of ranibizumab injections was 8.0 in the sham TTT group versus 6.3 in the TTT group (p0.05). The mean number of injections between 0-12 months and 13-24 months was 4.8 versus 4.6 (p0.05) and 3.2 versus 1.7 (p0.01) in the sham TTT and TTT groups, respectively. There was no statistically significant difference in BCVA (+4.0 vs +0.9 ETDRS letters), CRT (-49.9% vs -36.4%) or lesion area (-0.3% vs -10.6%) between the treatment groups at the final examination. The results of the intent-to-treat population (92 patients) were similar to the PP population.Treatment with low-dose TTT significantly reduced the number or intravitreal injections of ranibizumab over 24 months. The results suggest that low-dose TTT can serve as an adjuvant in combination with intravitreal ranibizumab for neovascular AMD.The trial is registered at http://clinicaltrials.gov (no NCT00599222).

Purpose. To evaluate the long-term visual results in central retinal vein occlusion (CRVO) following repeated intravitreal injections of bevacizumab (IVB). Methods. Thirteen patients (aged 34 to 79 years) with a duration of CRVO of 2 weeks to 6 months (mean 2.5 months) had a best-corrected visual acuity (BCVA) 0.05 to 0.4 (mean 0.13) as determined by Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Clinical examination was carried out at baseline and every 6 to 8 weeks. Intravitreal bevacizumab (1.25 mg) was given every 6 weeks during the first 6 months, and after that at the discretion of the attending physician. Results. In total, 96 IVB (average 7.4/patient) were given: 50 IVB during the first 6 months, 28 from 6 to 12 months, and 18 from 12 to 18 months. Average BCVA had improved 15 ETDRS letters at 3 months, 24 letters at 6 months, 24 letters at 12 months, and 18 letters at 18 months (p15 ETDRS letters at 12 months, and 7 subjects (54%) >15 ETDRS letters at 18 months. Foveal thickness decreased from 596 μm at baseline to 294 μm at 18 months (pConclusions. Following repeated IVB, there was a significant gain of BCVA during the follow-up of 18 months. To maintain visual gain, regular ophthalmologic examinations and repeated injections seem to be necessary as long as the disease is active.

HER3 is a member of the epidermal growth factor receptor (EGFR) family and is expressed in several types of cancer. Both the cytoplasmic and nuclear appearances of the receptor have been reported. Here, we investigate the expression and subcellular distribution of HER3 in uveal melanoma (UM) cells and tissues and its potential impact on clinical outcome of patients. Paraffin-embedded samples from 128 consecutive UM patients, enucleated without alternative treatment on UM diagnosis, were evaluated for HER3 using immunohistochemistry. Immunoreactivity was scored for frequency, intensity of positive cells, and subcellular distribution. The results were correlated with the established clinicopathological parameters using univariate and multivariate statistical analyses. HER3 expression was shown in 70% of the cases (89/128). This contrasts with the other EGFR family receptors (EGFR, HER2 and HER4) that are infrequently expressed in UM. Surprisingly, HER3 was found to be localized solely in the cell nuclei in 56 cases. The remaining 33 HER3 positive cases showed diffuse distribution (cytoplasmic ± nuclear). Nuclear HER3 was independently correlated with a more favorable overall survival (p = 0.043 and hazard ratio = 0.618) compared to cases with diffuse and/or no HER3. Nuclear localization of HER3 was also confirmed in fresh UM material and in UM cell lines. In conclusion, HER3 is frequently localized solely in the cell nuclei in UM and as such it predicts a more favorable overall survival.

Acta Ophthalmol. 2010: 88: 836–841 Abstract. Purpose: To perform a prospective study on central retinal vein occlusion (CRVO) to evaluate whether visual acuity can be improved and macular oedema reduced in response to intravitreal injections of bevacizumab. Methods: The case material comprised 13 patients (aged 34–79 years), duration of CRVO was 2 weeks to 6 months, baseline ETDRS visual acuity 0.06–0.4 (mean Snellen 0.13, derived from logMAR value) and intraocular pressure (IOP) 12–20 (mean 15.2) mmHg. Clinical examination, including optical coherence tomography (OCT), was carried out at baseline and every 6 weeks, digital fluorescein angiography at baseline, at 3 months and 6 months. Intravitreal injections of bevacizumab (1.25 mg) were given under microscopic control at baseline and every 6 weeks during the 6-month follow-up. Results: Following one intravitreal injection of bevacizumab, average visual acuity improved by 13 ETDRS letters at 1 month (p

Although there are no randomised trials directly comparing topical chemotherapeutic agents mitomycin-C, 5-fluorouracil, and interferon-alpha2b, published studies indicate equal efficacy of these agents for treatment of non-invasive ocular surface squamous neoplasia (80%-88%). 5-Fluorouracil may be preferred, given low incidence of serious side effects and low cost to the patient.

Purpose: We aimed to report a case of orbital solitary fibrous tumour (SFT) in a child and to review the relevant literature. Methods: We describe an SFT in a 13-year-old boy with a 1-month history of painless proptosis in the left eye. Results: Magnetic resonance imaging revealed a well circumscribed mass filling most of the left intraconal orbit. The lesion was excised and histopathological examination revealed a malignant SFT. Postoperative follow-up for 18 months was uneventful. Conclusions: Malignant SFT of the orbit should be included in the differential diagnosis of paediatric orbital tumours. Complete surgical excision remains the preferred method of management and the longterm prognosis is guarded.

Most previous reports on survival following enucleation for uveal malignant melanoma do not contain cumulative survival rates, do not use a multivariate approach and are liable to a considerable loss to follow-up. In this study, the long-term survival and tumour-related mortality were studied in 340 patients. Archival specimens containing posterior uveal melanomas were initially examined and sectioned by one pathologist. There was no loss to follow-up 6 to 22 years after enucleation. At the end of study, 233 (68.5%) individuals were dead; 137 (40.3%) of melanoma-related causes and 96 (28.2%) of other causes. Melanoma-related deaths appeared from 24 to 6848 days (18 years 8 months) after enucleation. The cumulative 5-year survival proportion based on melanoma-related deaths was 70% and the corresponding 10-year proportion was 56%. Multivariate Cox regression indicated that the largest tumour dimension, cell type, and tumour location all had independent prognostic value, the associated hazard ratios ranged from 1.2 to 1.4, suggesting a moderate increase of the relative risk. Pair-wise comparisons of the parameters indicated that large tumours were more common in the anterior choroid or ciliary body than in the posterior choroid. Similarly, large tumours were more often necrotic, composed of epitheloid cells, or featured extrascleral extension. Tumours with significant scleral invasion or extrascleral extension were more common in elderly patients.

The Swedish experience of ruthenium 106 plaque radiotherapy for posterior uveal melanoma includes 266 patients treated between 1979 and 1995. The median dose delivered at the tumour apex was 100 Gy and the median follow-up after radiotherapy was 3.6 years (range = 0.5 to 12.5 years) with no patient being lost to follow-up. Visual acuity deteriorated moderately following treatment but appeared to stabilize after 5 to 6 years. Treatment failure defined as enucleation following plaque treatment occurred in 46 of the 266 (17%) studied patients. The cumulative 5-year probability of retaining the eye after radiotherapy was 82% and by univariate analysis tumour height, tumour diameter and tumour stage each predicted subsequent treatment failure, whereas in multivariate analysis no single covariate retained a predictive value. Forty-five of the 266 patients died of any cause during follow-up; 27 of these deaths were melanoma-related. The cumulative 5-year survival proportion (based on melanoma-related deaths only) was 86%. Death in metastatic disease appeared to be more common among patients that failed ruthenium plaque radiotherapy, however these patients also tended to have large tumours.

Corneal integrity is dependent on a constant turnover of epithelial cells. According to the current hypothesis essential contributors to this process, the so-called stem-cells, are localized in the limbal area of the cornea. However, histological identification of stem cells of the cornea is thus far not possible. In the present study we have used specific antibodies against proliferating cell nuclear antigen (PCNA). The nuclear protein is expressed in cells during replication. Prior to establishment of staining indices the optimal fixation procedure was found to be of major importance for the results and standardized for fixation in 4% formaldehyde. This procedure also gave the best preservation of the morphology. In the corneas of ten New Zealand rabbits the staining index for PCNA was found to be on average 23% (SD ± 13%) for the basal layer of the limbal epithelium. In the mid-peripheral and central corneal epithelium only occasional staining of PCNA was detected with a 2% staining index (SD ± 2%). The agglomeration of PCNA-positive cells in the basal layer of the limbal epithelium together with their colocalization with the known location of stem cells strongly suggests that PCNA could serve as a reliable indicator for the proximity of proliferating corneal epithelial stem cells in histological sections, which would be of significant clinical importance.

A case of ocular melanocytosis with the simultaneous occurrence of a choroidal malignant melanoma, a ciliary body melanocytoma and a surface plaque iris naevus in an 80-year-old male Caucasian is reported. Patients with ocular or oculodermal melanocytosis are considered to be at risk for tumour formation and malignant transformation; the multiple melanocytic tumours of the present case support this hypothesis.

Enucleation following ruthenium plaque radiotherapy for posterior uveal melanoma indicates failure of treatment. This study focused on the histopathological findings and remaining tumour cell growth fraction in 42 of 46 patients with failed ruthenium plaque treatment (of 266 patients treated) for melanoma of the choroid or ciliary body. The cause for enucleation was clinically detected tumour regrowth in 27 (64%) patients, treatment-related ocular side effects in 12 (29%) cases and the patient's personal preference in three (7%) cases. The median time elapsing from plaque radiotherapy to enucleation was not significantly different for patients with recurrent tumour growth (23 months) compared to those enucleated without clinical signs of regrowth (19 months). While all tumours showed some regressive features by histopathological examination, only five melanomas were completely necrotic and viable-appearing tumours cells were present in all of the remaining 37 (88%) irradiated tumours. Microwave processed PC-10 immunostainings increased the sensitivity to detect cycling cells compared to the sole use of mitotic cell counts. By the former technique, proliferating tumour cells were detected in 17 of 23 (74%) studied melanomas of eyes enucleated for tumour regrowth following brachytherapy. Also, the number of cycling melanoma cells was similar to that of non-irradiated controls managed solely by enucleation. In contrast, the proliferative compartments of irradiated, but non-recurrent, posterior uveal melanomas were significantly reduced compared to those of matched controls. Still, cycling tumour cells were present in four of 13 (31%) irradiated melanomas, clinically assumed to be successfully treated.

Purpose: To compare the effects of low-dose transpupillary thermotherapy (TTT) and verteporfin photodynamic therapy (PDT) on patient-reported visual function using the National Eye Institute Visual Function Questionnaire 25 (NEI VFQ-25) in patients with occult neovascular age-related macular degeneration (AMD). Methods: Patients were randomized to receive either low-dose TTT (and sham PDT) (n = 52) or PDT (and sham TTT) (n = 46). Patients were followed for 12 months with retreatment according to clinical assessment. The clinical outcome of this study has been recently reported. The NEI VFQ-25 questionnaire was administered at baseline and at 12 months. Results: Forty-two patients (80.1%) in the TTT group and 37 patients (80.0%) in the PDT group completed the questionnaire at the 12-month follow-up. The mean change in the NEI VFQ-25 composite score was +1.2 for the TTT group (p > 0.05) and +0.7 for PDT group (p > 0.05). None of the subscale categories showed significant changes between treatment groups at 12 months. Subgroup analysis showed that NEI VFQ-25 scores were lower in patients treated in their better-seeing eye. Conclusion: In this randomized study on patients with occult neovascular AMD, low-dose TTT and PDT appeared to be equally potent at stabilizing patient-reported visual function. However, the study was underpowered for this conclusion to be made firmly. Also, given the impressive results obtained with ranibizumab for all types of neovascular AMD, neither PDT nor low-dose TTT should be considered as first-line treatments.

The cyclolignan picropodophyllin (PPP) efficiently blocks the activity of insulinlike growth factor-1 receptor (IGF-1R) and inhibits the growth of uveal melanoma cells in vitro and in vivo. In this study, the authors investigated the efficiency of orally administered PPP on the growth of uveal melanoma xenografts. In addition, they focused on the effect of PPP on vascular endothelial growth factor (VEGF) in vivo and evaluated its effects in combination with other established antitumor agents in vitro.Four different uveal melanoma cell lines (OCM-1, OCM-3, OCM-8, 92-1) were treated with PPP alone and in combination with imatinib mesylate, cisplatin, 5-fluorouracil, and doxorubicin. Cell viability was determined by XTT assay. SCID mice that underwent xenografting with uveal melanoma cells were used to determine antitumor efficacy of oral PPP in vivo. Five mice were used per group. Tumor samples obtained from the in vivo experiments were analyzed for VEGF and IGF-1R expression by Western blotting.PPP was found to be superior to the other antitumor agents in killing uveal melanoma cells in all four cell lines (IC500.05 microM). Oral PPP inhibited uveal melanoma growth in vivo in OCM-3 (P = 0.03) and OCM-8 (P = 0.01) xenografts and was well tolerated by the animals. PPP decreased VEGF expression in the OCM-1 (P = 0.006) and OCM-8 (P = 0.01) tumors.Oral PPP was well tolerated in vivo, caused total growth inhibition of uveal melanoma xenografts, and decreased VEGF levels in the tumors.

Introduction Choroidal neovascularization (CNV) is a debilitating complication of age-related macular degeneration (AMD) and a leading cause of vision loss. Along with other angiogenic factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF)-1 and its receptor, IGF-1R, have been implicated in CNV. Purpose A prior study has shown that the cyclolignan picropodophyllin (PPP) efficiently blocks the insulin-like growth factor-1 receptor (IGF-1R) activity and causes cell death in uveal melanoma cell lines and in an in vivo model. In this study we investigated the effect of PPP on VEGF expression, both in vitro and in vivo, and whether this effect has antiangiogenic consequences in a murine CNV model. Methods C57BL/6J mice with laser-induced CNVs were treated with PPP. Effects on CNV area were assayed by image analysis. VEGF levels in the choroid and retinal pigment epithelial cells (ARPE-19) were measured by Western blot or ELISA. Transcriptional activation of the VEGF promoter was determined by luciferase reporter gene assay. Results Mice treated with PPP, administered intraperitoneally or orally, showed a 22% to 32% (P = 0.002) decrease in CNV area. Furthermore, VEGF levels in the choroid were significantly reduced. In cultured ARPE-19 cells, IGF-1 was shown to increase VEGF secretion. This increase was completely blocked by PPP. PPP reduced the level of transcriptional activity of the VEGF promoter. Conclusions PPP reduces IGF-1-dependent VEGF expression and CNV in vivo. Accordingly, IGF-1R inhibitors may be useful tools in the treatment of conditions associated with CNV, including neovascular AMD.

Aside from melanocytic, vascular, and lymphocytic neoplasias of the uvea and tumors metastatic to the uvea, there are a few far less frequent and diverse, but distinct, forms of uveal tumors. These ot

This chapter provides information about the tumours of the eye and orbit, including benign and malignant lesions of the conjunctiva and ocular adnexa as well as intraocular tumours, such as uveal melanoma, vascular tumours, and lymphoma of the retina and CNS. The chapter also provides information on the symptoms and signs of such lesions, the recommended examination and imaging procedures, the principles of management and treatment, assessment of quality of life, as well as on prognosis, histopathology, differential diagnoses, and molecular biology. Each section discusses not only optimal potentially curative management, but also long-term follow-up and maintenance of vision.

PURPOSE: To study the safety of irrigation with 5-fluorouracil (5-FU) in the Perfect Capsule sealed-capsule irrigation device (Milvella, Ltd., Epping, Australia). SETTING: St. Erik's Eye Hospital, Stockholm, Sweden. METHODS: Thirty 8-week-old rabbits were divided into 4 groups. Clear lens extraction was performed and the Perfect Capsule was applied in 1 eye in Groups 1, 2 and 3. The sealed system was flushed with balanced salt solution (BSS) in Group 1, 5-FU 50 mg/mL in Group 2, and 5-FU followed by BSS in Group 3. In Group 4, the Perfect Capsule was not applied; instead, 0.2 mL of 5-FU was instilled in the capsule and left there for 30 seconds. An endothelial cell count and pachymetry were performed preoperatively and 24 hours postoperatively. At 24 or 48 hours (half of each group at each time point), the rabbits were killed and the retina and trabecular meshwork histopathologically examined. The endothelial cell count and pachymetry were compared between the Perfect Capsule eye and the control eye in Group 1. RESULTS: There was no difference between the groups in endothelial cell count (P = .96) or pachymetry (P = .32). Histologic evaluation showed no damage from the 5-FU. The comparison between eyes in Group 1 showed that the use of the Perfect Capsule did not cause more endothelial cell loss (P = .86) or increase pachymetry more (P = .28) than in the control eye. CONCLUSION: Irrigation with 5-FU 50 mg/mL in the sealed-capsule irrigation device was safe and caused no apparent damage to the adjacent intraocular tissues.

PurposeTo assess of the effect of local recurrence of uveal melanoma on metastasis using a multicenter international tumor registry.DesignRetrospective study using an online tumor registry.ParticipantsPatients with uveal melanoma diagnosed between 2001 and 2011.MethodsA committee was formed to create uveal melanoma patient-specific data fields. Ten subspecialty ophthalmic oncology centers from 4 continents shared data. Patient selection criteria included diagnosis of uveal melanoma and adequate records to allow tumor staging by American Joint Committee on Cancer (AJCC) criteria and follow-up for metastatic melanoma.Main Outcome MeasuresLocal tumor recurrence and metastatic uveal melanoma.ResultsOf 3809 total entries, 3217 patients with ciliary body and choroidal (CBC) melanoma and 160 with iris melanoma were evaluated. There was a median follow-up of 3.7 years (95% confidence interval [CI], 3.5–3.8). One hundred fifty-two patients (4.7%) with CBC melanoma experienced local recurrence, with a cumulative incidence of 11%. Kaplan-Meier point estimates for remaining free of local recurrence were 99% (95% CI, 99–99) at 1 year, 93% (95% CI, 92–94) at 5 years, and 89% (95% CI, 86–91) at 10 years. Five- and 10-year metastasis-free Kaplan-Meier estimates for the recurrence-free group were 87% (95% CI, 86–89) and 82% (95% CI, 79–84), and those for the local recurrence group were 71% (95% CI, 62–78) and 62% (95% CI, 49–72). The difference between these 2 groups was statistically significant (P < 0.001). Furthermore, local tumor recurrence increased the risk of metastasis by a hazard ratio (HR) of 6.28 (95% CI, 4.4–8.9; P < 0.001). Local recurrence was detected up to 9.8 years after treatment. Extrascleral extension also was associated with local recurrence (HR, 3.2; 95% CI, 1.5–6.7; P = 0.003), but higher AJCC T-size category was not (P = 0.63). Five patients (n = 5/161 [3.1%]) with iris melanoma demonstrated local recurrence and 1 metastasized.ConclusionsInternational multicenter data sharing was used to evaluate the effect of local tumor recurrence on metastatic rate. In that local tumor recurrence was associated with a significantly higher risk of systemic metastasis, effective initial treatment and long-term surveillance of treated uveal melanoma patients is necessary.

Age-related macular degeneration (AMD), the most common cause of visual loss after the age of 65, displays a degeneration of the retinal pigment epithelial (RPE) cells and photoreceptors in the retinal centre (macula). The central macula (fovea) that contains mostly cone photoreceptors mediates the high visual acuity. Drusen maculopathy may lead to visual deterioration. Drusen are extracellular deposits of debris that accumulate on Bruch's membrane. Drusen attract inflammatory, immunological and vasoactive stimuli. RPE and photoreceptor cells overlying drusen exhibit biochemical and morphological signs of degeneration. Strong and intermittent light exposure (photons) induces the formation of free radicals in the very high oxygen tension milieu of the retina. The negative effects of irradiation stimulate accumulation of lipofuscin in RPE and photoreceptor cells leading to mitochondrial dysfunction and apoptotic cell death. A hydrophobic barrier is built up in Bruch's membrane reducing diffusion to the choroid. Hereditary and inflammatory factors modify the risk for AMD. There is a genetic dysregulation of the complement system leading to inappropriate complement activation. The genetic polymorphism of complement factor H (CFH) and age-related maculopathy susceptibilty 2 (ARMS2) increase the risk of progression to advanced AMD. The photoelectric effect creates free radicals, resulting in a continuous increase of lipofuscin formation and impairing mitochondrial activity. In addition, inflammation and complement dysregulation contribute to the formation of drusen and vasoproliferative reactions with neovascularization. Antioxidants neutralize reactive oxygen species and reduce lipofuscin accumulation in RPE and photoreceptor cells. For prophylactic treatment of drusen maculopathy, high doses of antioxidants such as vitamins C and E, lutein, zeaxanthine and zinc are used according to the Age-Related Eye Disease Study 2 (AREDS 2). The risk of developing advanced AMD was reduced by 27% at 10 years follow-up. No adverse events were noted.

Although an accurate uveal melanoma staging system is needed to improve research and patient care, the evaluation of eye cancer staging systems requires international multicenter data sharing to acquire a statistically significant analysis.To assess patient mortality outcomes associated with uveal melanoma staging according to the 7th edition of the American Joint Committee on Cancer's AJCC Cancer Staging Manual.A committee was formed to create patient-specific data fields for patients with uveal melanoma. Ten subspecialty ophthalmic oncology centers from 4 continents shared data. Patient selection criteria included diagnosis of uveal melanoma from April 1, 2001, to April 1, 2011, adequate records to allow tumor staging by the AJCC criteria, and follow-up for metastatic melanoma.Primary treatments included local resection, radiation therapy, and enucleation.Metastasis after initial tumor staging with 5- and 10-year Kaplan-Meier metastasis-free point estimates, depending on AJCC prognostic stages I through IV, tumor size category, and subclassification (defined by the presence of ciliary body involvement and/or extrascleral extension).A total of 3809 patients were entered into the database. Of these, 3377 records (88.7%) were complete. Primary ciliary body and choroidal melanoma was the diagnosis for 3217, and 160 had primary iris melanoma. Tumor size categories were T1 in 1115 (34.7%) of the 3217 patients, T2 in 1128 patients (35.1%), T3 in 789 patients (24.5%), and T4 in 185 patients (5.8%). The 5- and 10-year Kaplan-Meier metastasis-free point estimates by tumor size categories were 97% (95% CI, 95%-98%) and 94% (95% CI, 91%-96%) for T1 tumors, 85% (95% CI, 82%-88%) and 80% (95% CI, 75%-84%) for T2 tumors, 77% (95% CI, 73%-80%) and 68% (95% CI, 60%-74%) for T3 tumors, and 61% (95% CI, 49%-71%) (5-year only) for T4 tumors, respectively. Increasing tumor size was consistent with increased metastasis risk (P .001). Subclassifications were significantly associated with increased risk of metastasis (P.001). The AJCC prognostic and anatomical groupings were as follows: stage I, 1030 (32.0%); stage IIA, 1095 (34.0%); stage IIB, 710 (22.1%); stage IIIA, 282 (8.8%); stage IIIB, 79 (2.5%); and stage IIIC, 21 (0.7%). The 5- and 10-year Kaplan-Meier metastasis-free estimates for prognostic stages were 97% (95% CI, 95%-98%) and 94% (95% CI, 91%-96%) for stage I, 89% (95% CI, 86%-91%) and 84% (95% CI, 80%-88%) for stage IIA, 79% (95% CI, 75%-83%) and 70% (95% CI, 62%-76%) for stage IIB, 67% (95% CI, 59%-73%) and 60% (95% CI, 51%-68%) for stage IIIA, 50% (95% CI, 33%-65%) and 50% (95% CI, 33%-65%) for stage IIIB, and 25% (95% CI, 4%-53%) (5-year only) for stage IIIC, respectively. The 160 iris melanomas were too few for subgroup analysis.Multicenter, worldwide, Internet-based data sharing was used to study a heterogenous patient population in ophthalmic oncology. Our results support the continued use of the 7th edition of the AJCCCancer Staging Manual for uveal melanoma.

The pathogenesis of age-related maculopathy (ARM), the most common cause of visual loss after the age of 60 years, is indeed a complicated scenario that involves a variety of hereditary and environmental factors. The pathological cellular and molecular events underlying retinal photochemical light damage, including photoreceptor apoptosis, have been analysed in experimental animal models. Studies of age-related alterations of the retina and photoreceptors, the accumulation of lipofuscin in retinal pigment epithelium (RPE) cells, and the formation of drusen have greatly contributed to our knowledge. A new concept of an inflammatory response to drusen has emerged, suggesting immunogenic and systemic reactions in Bruch's membrane and the subretinal space. Oxidative stress and free radical damage also impact on the photoreceptors and RPE cells in the ageing eye. Based on the photoelectric effect, a fundamental concept in quantum physics, the consequences of high-energy irradiation have been analysed in animal models and cell culture. Short-wavelength radiation (rhodopsin spectrum), and the blue light hazard (excitation peak 440 nm), have been shown to have a major impact on photoreceptor and RPE function, inducing photochemical damage and apoptotic cell death. Following cataract surgery, there is a dramatic change in ocular transmittance. In aphakic or pseudophakic eyes (with clear intraocular lenses), high-energy (blue) and ultraviolet-A radiation strikes the retina. Epidemiological data indicate a significantly increased 5-year incidence of late ARM in non-phakic eyes compared with phakic eyes. In recent years, putative prophylactic measures against ARM have emerged. The implantation of 'yellow' intraocular lenses (IOLs) that absorb high-energy blue radiation is, from a theoretical point of view, the most rational approach, and, from a practical point of view, is easy to accomplish. With increasing age, RPE cells accumulate lipofuscin (chromophore A2E). It is noteworthy that the yellow IOL not only protects A2E-laden human RPE cells from blue light (peak 430 nm) damage, but also alleviates the detrimental effects of green (peak 550 nm) and white light. A prophylactic treatment using antioxidants is aimed at counteracting oxidative stress and free radical cellular damage. The Age-Related Eye Disease Study (AREDS), a randomized clinical trial, showed a significantly lower incidence of late ARM in a cohort of patients with drusen maculopathy treated with high doses of antioxidants than in a placebo group. In recent years, considerable progress in retinal research has been achieved, creating a platform for the search for new prophylactic and therapeutic measures to alleviate or prevent photoreceptor and RPE degeneration in ARM.

Nordic ophthalmologists and vision scientists are active in many fields of eye research. This is most evident at the biannual Nordic Congress of Ophthalmology, most recently held in Malmo in June 2004. The authors here review some of the research in vision and ophthalmology presented at this meeting or published recently by Nordic scientists. This paper does not represent a comprehensive review of all Nordic research in the field, but attempts to give an overview of some of the activities underway in eye research in this part of the world.

Objective: To evaluate the recurrence rate, reoperation rate and side-effects of a novel technique for pterygium surgery. Design: Retrospective study. Participants: The study included 461 eyes of 381 patients operated for primary nasal pterygium by the same surgeon between 1994 and 2003 and followed for 23 ± 20 months (range 6–112 months). Methods: Autologous conjunctival grafts harvested at the superotemporal limbus were used to cover the sclera after pterygium excision. Using a retrospective chart review, the outcome after attaching the transplant to the sclera with a fibrin tissue adhesive (n = 325) was compared to the outcome after graft attachment using absorbable sutures (n = 136). Main outcome measures: Recurrence rate, reoperation rate and complications. Results: The recurrence rate was 5.3% in the glue group and 13.5% in the suture group (p = 0.01). The reoperation rates were 1.2% and 3.3%, respectively (p = 0.31). Complications, such as transient transplant oedema and persistent corneal epithelial defects, occurred equally in both groups. Conclusion: Using a fibrin tissue adhesive instead of sutures when attaching the conjunctival transplant in primary pterygium surgery results in a significantly lower recurrence rate.

Earlier studies have suggested a role for metalloproteinase-2 (MMP-2) in retinal angiogenesis. To investigate this further, we have studied retinal vascular development and pathologic ischemia-induced retinal angiogenesis in MMP-2-deficient and wild-type mice.Vascular development of the retina was studied in retinal flatmounts, whereas pathologic retinal angiogenesis was analyzed in retinal flatmounts and on histologic sections using a model of ischemia-induced retinopathy. The time course of MMP-2 mRNA expression was determined by in situ hybridization and real-time polymerase chain reaction (PCR).Formation of the retinal vascular plexus was not significantly different in MMP-2-deficient mice as compared to wild-type mice. In ischemia-induced retinopathy, there was an increased formation of extraretinal neovascular tufts in the MMP-2-deficient mice (p0.05). MMP-2 mRNA expression did not correlate to either retinal vascular development or to ischemia-induced formation of extraretinal vascular tufts.The current data suggest that MMP-2 is not essential for either retinal vascular development or pathologic retinal neovascularization in the mouse.