Aquaporin-1 Expression in Retinal Pigment Epithelial Cells Overlying Retinal Drusen.

PURPOSE: In the outer retina, age-related macular degeneration (AMD) results in reduced hydraulic conductivity in Bruch's membrane, possibly leading to altered water transport in retinal pigment epithelial (RPE) cells. We hypothesize that RPE cells may express aquaporin-1 (AQP1) to compensate for these changes. Therefore, we wanted to investigate the expression of AQP1 in RPE cells of human eyes with age-related maculopathy (ARM) and AMD, and eyes with tumour-associated drusen. METHODS: Nine human eyes with ARM, 6 eyes with AMD and 9 eyes with choroidal malignant melanoma were examined for immunoreactivity to AQP1. AQP1 labelling in the RPE cells was evaluated for each drusen and grouped according to size and AQP1 labelling. AQP1 labelling in the RPE outside drusen was also evaluated. RESULTS: AQP1 labelling was observed in the apical membrane of the RPE cells situated above drusen in all three groups. There was a significant association between AQP1 labelling and drusen size (p < 0.001), and AQP1 labelling was more frequently observed in large drusen. CONCLUSION: AQP1 was expressed in RPE cells covering drusen but not in RPE cells outside drusen. We suggest that AQP1 expression is upregulated in the cell membranes of RPE cells above drusen in order to alleviate the increased need for fluid transport across the growing drusen.

Nodular hidradenoma of the caruncle.

An 84-year-old man presented with a tumor of the right caruncle causing epiphora due to insufficient eyelid closure. The tumor was cystic and mucinous in appearance. MRI showed a solitary tumor of the caruncle with no adhesions to neighboring tissue. The mass was removed by carunculectomy. Histopathologic examination revealed a tumor composed of epithelial cells with intervening strands of hyalinized stroma. Solid areas were predominant but a cribriform area could also be distinguished. Periodic acid-Schiff positive, diastase-labile material (glycogen) was detected in many tumor cells. Immunohistochemical staining of the tumor cells demonstrated positive staining with antibodies against CK-CAM 5.2, BER-EP4, p63, and smooth muscle actin-positive cells in some areas. The tumor was diagnosed as a nodular hidradenoma of the caruncle, which has never been reported before and should be included in the diagnoses of caruncular tumors.

Functional recovery after experimental RPE debridement, mfERG studies in a porcine model.

BACKGROUND: The correlation between histologically identified regeneration of retinal pigment epithelium (RPE) and functional outcome measured by multifocal electroretinography (mfERG) following surgical debridement is examined in a porcine model. In humans, visual acuity is reduced in diseases with RPE loss such as RPE tears and geographic atrophy. Hypopigmented RPE is known to cover the lesion after RPE debridement in the pig, but it is unclear whether this leads to a return of photoreceptor function. METHODS: RPE debridement was performed in ten pigs by vitrectomy and retinotomy, and by brushing the Bruch's membrane with a silicone catheter. Immediately following surgery (baseline) and after 2 and 6 weeks respectively, the animals were examined by mfERG, fundus photographs (FPs), fluorescein angiograms (FAs), and histopathology. RESULTS: The mfERG P1 amplitude was decreased 2 weeks (T2) after surgery; it returned to baseline 6 weeks (T6) after surgery. FPs, FAs, and histology showed partial repopulation of Bruch's membrane by hypopigmented RPE cells and atrophied outer segments at T2. At T6, normally pigmented RPE cells were identified, and the photoreceptor layer was restored. CONCLUSION: This is the first study to show that the histological regeneration of hypopigmented RPE correlates to a return of the retinal function, measured by mfERG.

Monocular visual deprivation suppresses excitability in adult human visual cortex.

The adult visual cortex maintains a substantial potential for plasticity in response to a change in visual input. For instance, transcranial magnetic stimulation (TMS) studies have shown that binocular deprivation (BD) increases the cortical excitability for inducing phosphenes with TMS. Here, we employed TMS to trace plastic changes in adult visual cortex before, during, and after 48 h of monocular deprivation (MD) of the right dominant eye. In healthy adult volunteers, MD-induced changes in visual cortex excitability were probed with paired-pulse TMS applied to the left and right occipital cortex. Stimulus-response curves were constructed by recording the intensity of the reported phosphenes evoked in the contralateral visual field at range of TMS intensities. Phosphene measurements revealed that MD produced a rapid and robust decrease in cortical excitability relative to a control condition without MD. The cortical excitability returned to preinterventional baseline levels within 3 h after the end of MD. The results show that in contrast to the excitability increase in response to BD, MD acutely triggers a reversible decrease in visual cortical excitability. This shows that the pattern of visual deprivation has a substantial impact on experience-dependent plasticity of the human visual cortex.

Malignant transformation of a medulloepithelioma of the optic nerve.

OBJECTIVE: To describe a case of malignant transformation of a medulloepithelioma of the optic nerve. METHODS: A 3-year-old boy presented with right-sided proptosis, swollen eyelids, restricted ocular movements, pain and nausea. Visual acuity was hand motions. A benign non-teratoid medulloepithelioma of the optic nerve was surgically removed. Due to relapse in the orbit 10 months postoperatively enucleation and partial orbital exenteration were performed. Light microscopy and immunohistochemistry now revealed a malignant medulloepithelioma. The boy was further treated with chemotherapy and radiotherapy and is still alive 36 months after primary surgery. RESULTS: Medulloepithelioma of the optic nerve is extremely rare. Only eight cases have been described in the literature. Unlike intraocular medulloepithelioma, all have been malignant tumours. This is the first case described of a benign medulloepithelioma of the optic nerve, later transforming into a malignant tumour. One third of patients with medulloepithelioma of the optic nerve have died from direct intracranial spread or metastasis to the central nervous system (CNS). CONCLUSIONS: Medulloepithelioma of the optic nerve should be considered malignant despite morphology with tendency to spread to the CNS. Furthermore; it should be considered as a differential diagnosis when observing a tumour of the optic nerve in a child.

Ocular proteomics with emphasis on two-dimensional gel electrophoresis and mass spectrometry.

The intention of this review is to provide an overview of current methodologies employed in the rapidly developing field of ocular proteomics with emphasis on sample preparation, two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and mass spectrometry (MS). Appropriate sample preparation for the diverse range of cells and tissues of the eye is essential to ensure reliable results. Current methods of protein staining for 2D-PAGE, protein labelling for two-dimensional difference gel electrophoresis, gel-based expression analysis and protein identification by MS are summarised. The uses of gel-free MS-based strategies (MuDPIT, iTRAQ, ICAT and SILAC) are also discussed. Proteomic technologies promise to shed new light onto ocular disease processes that could lead to the discovery of strong novel biomarkers and therapeutic targets useful in many ophthalmic conditions.

Acute retinal ischemia caused by controlled low ocular perfusion pressure in a porcine model. Electrophysiological and histological characterisation.

The purpose of this study was to establish, and characterize a porcine model of acute, controlled retinal ischemia. The controlled retinal ischemia was produced by clamping the ocular perfusion pressure (OPP) in the left eye to 5 mm Hg for 2 h. The OPP was defined as mean arterial blood pressure (MAP) minus the intraocular pressure (IOP). It was clamped to 0-30 mm Hg by continuous monitoring of MAP and adjustment of the IOP, which was controlled by cannulation of the anterior chamber. Inner retinal function was assessed by induced multifocal electroretinography (mfERG) with comparisons of the amplitudes obtained in the experimental, left eye, and the control, right eye. Quantitative histology was performed to measure the survival of ganglion cells, amacrine cells and horizontal cells 2-6 weeks after the ischemic insult. An OPP of 5 mm Hg for 2h induced significant reductions in the amplitudes of iN1 to 20% (CI: 13-30%), and iP2 to 14% (95% CI: 8-22%) of their baseline values. No signs of recovery were found within the 6-week observation period. Quantitative histology revealed a highly significant reduction in the number of ganglion cells, amacrine cells and horizontal cells after the ischemic insult. This model seems to be suitable for investigations of therapeutic initiatives in diseases involving acute retinal ischemia.

Delayed administration of glial cell line-derived neurotrophic factor (GDNF) protects retinal ganglion cells in a pig model of acute retinal ischemia.

This study investigates whether intravitreal administration of glial cell line-derived neurotrophic factor (GDNF) enhances survival of NeuN positive retinal cells in a porcine model of retinal ischemia. 16 pigs were subjected to an ischemic insult where intraocular pressure was maintained at 5 mmHg below mean arterial blood pressure for 2 h. The mean IOP during the ischemic insult was 79.5 mmHg (s.e.m. 2.1 mmHg, n = 15). Three days after the insult the pigs received an intravitreal injection of GDNF microspheres or blank microspheres. The pigs were evaluated by way of multifocal electroretinography (mfERG), quantification of NeuN positive cells and evaluation of the degree of retinal perivasculitis and inflammation 6 weeks after the insult. In the post-injection eyes (days 14, 28 and 42), the ratios of the iN1 and the iP2 amplitudes were 0.10 (95% CI: 0.05-0.15) and 0.09 (95% CI: 0.04-0.16) in eyes treated with blank microspheres, and 0.24 (95% CI: 0.18-0.32) and 0.23 (95% CI: 0.15-0.33) in eyes treated with GDNF microspheres. These differences were statistically significant (P < 0.05). The number of NeuN positive cells in the area of the visual streak area was significantly higher in eyes injected with GDNF microspheres compared to eyes injected with blank microspheres. In eyes injected with GDNF microspheres the ganglion cell count was 9.5/field (s.e.m.: 2.1, n = 8), in eyes injected with blank microspheres it was 3.5/field (s.e.m.: 1.2, n = 7). This difference was statistically significant (P < 0.05). There was also a significant difference (P < 0.01) in the degree of perivasculiitis between GDNF treated eyes (median perivasculitis score 1.5) and blank treated eyes (median perivasculitis score 3.0). In conclusion, injection of GDNF microspheres 3 days after an ischemic insult results in functional and morphological rescue of NeuN positive cells in a porcine model of acute ocular ischemia.

Chemokine Expression in Murine RPE/Choroid in Response to Systemic Viral Infection and Elevated Levels of Circulating Interferon-γ.

Purpose: To examine how circulating immune mediators in vivo may affect gene and protein expression at the RPE/choroid interface. Methods: Young mice were systemically infected with lymphocytic choriomeningitis virus (LCMV) or continuously infused with IFN-γ. RPE/choroid was isolated and analyzed with whole-transcriptome gene expression microarrays. Selected gene expression findings were validated at the protein level. Results: Both the systemic immune activation from virus infection and the sterile systemically increased level of IFN-γ resulted in increased expression of chemokine ligands, chemokine receptors, and early complement components in isolates of RPE/choroid. These findings were largely absent from LCMV-infected mice deficient in either the interferon α/ß receptor or IFN-γ. Conclusions: Together, these findings demonstrate that acute systemic immune activation results in a local response at the RPE/choroid interface that may include chemokine-dependent recruitment of inflammatory cells and engagement of the complement system. This may represent a link between the systemic low-grade inflammation and the retinal pathology observed in several multifactorial entities such as aging, AMD, and diabetes.

Signet ring cell carcinoma of the eyelid - the monocle tumour.

We report the clinical and histopathological characteristics of two cases of signet ring cell carcinoma of the eye lids, and discuss the histogenesis of this neoplasm. Two 72-year-old Caucasian males both presented with slowly growing tumours of the eyelids. The tumours were excised and specimens were examined using light- and transmission electron microscopic techniques. Clinically, the tumours infiltrated both eyelids on one side of the face with swelling and periocular inflammation, creating a monocle-like appearance. Extensive clinical work-up excluded periocular metastases. Histopathologically, the tumours were composed of rather bland cells with mainly histiocytoid morphology. A minor proportion had a signet ring cell appearance. The cytoplasmic inclusions giving the signet ring morphology were PAS- and colloidal iron positive. The tumour cells reacted with antibodies against cytokeratins, carcinoembryonic antigen, epithelial membrane antigen, gross cystic disease fluid protein-15 and lysozyme. Transmission electron microscopy demonstrated tumour cells containing intracytoplasmic vacuoles lined by microvilli. The tumour cells aggregated in duct-like clusters. A diagnosis of primary signet ring cell carcinoma was made in both cases. Histopathological, immunohistological and ultrastructural findings indicated that the tumours were of sweat gland origin.

Identification of intracellular phospholipases A2 in the human eye: involvement in phagocytosis of photoreceptor outer segments.

PURPOSE: To identify intracellular phospholipases A(2) (PLA(2)) in the human retina and to explore the role of these enzymes in human retinal pigment epithelium (RPE) phagocytosis of photoreceptor outer segments (POS). METHODS: PCR amplification and Western blot analysis were used to identify mRNA and protein expression of intracellular PLA(2) subtypes in the retinal pigment epithelial cell line ARPE-19. Immunohistochemical staining of normal human eye sections was performed to reveal the cellular location of the enzymes. A model of RPE phagocytosis of POS was used to explore the role of intracellular PLA(2) in phagocytosis. An activity assay was used to evaluate PLA(2) activity, and inhibitors of specific PLA(2) were applied to evaluate the role of PLA(2) in RPE phagocytosis. RESULTS: Genes encoding calcium-independent (i)PLA(2), group VIA; calcium-dependent cytosolic (c)PLA(2), groups IVA, IVB, and IVC; and iPLA(2), group VIB, were identified in the human RPE cell line ARPE-19. Furthermore, protein of iPLA(2)-VIA, cPLA(2)-IVA, and iPLA(2)-VIB were identified in ARPE-19 cells and in various parts of the normal human eye. iPLA(2)-VIA protein levels were upregulated during phagocytosis, and iPLA(2)-VIA activity was found to be specifically increased 12 hours after ARPE-19 cells were fed with POS. Finally, RPE phagocytosis was inhibited by the iPLA(2)-VIA inhibitor bromoenol lactone. CONCLUSIONS: Various intracellular PLA(2) subtypes are present in the human retina. iPLA(2)-VIA may play an important role in the regulation of RPE phagocytosis of POS and may also be involved in the regulation of photoreceptor cell renewal.

Optic nerve invasion of uveal melanoma.

The aim of the study was to identify the histopathological characteristics associated with the invasion of the optic nerve of uveal melanoma and to evaluate the association between invasion of the optic nerve and survival. In order to achieve this, all uveal melanomas with optic nerve invasion in Denmark between 1942 and 2001 were reviewed (n=157). Histopathological characteristics and depth of optic nerve invasion were recorded. The material was compared with a control material from the same period consisting of 85 cases randomly drawn from all choroidal/ciliary body melanomas without optic nerve invasion. Prelaminar/laminar optic nerve invasion was in multivariate analysis associated with focal retinal invasion, neovascularization of the chamber angle, and scleral invasion. Postlaminar invasion was further associated with non-spindle cell type and rupture of the inner limiting membrane of the retina. The optic nerve was invaded in four different ways: 1) by tumor extension from the neuroretina through the lamina cribrosa; 2) by direct extension into the optic nerve head between Bruch's membrane and the border tissue of Elschnig; 3) by direct invasion through the border tissue of Elschnig; and 4) in one case a tumor spread along the inner limiting membrane to the optic nerve through the lamina cribrosa. Invasion of the optic nerve had no impact on all-cause mortality or melanoma-related mortality in multivariate analyses. The majority of melanomas invading the optic nerve are large juxtapapillary tumors invading the optic nerve because of simple proximity to the nerve. A neurotropic subtype invades the optic nerve and retina in a diffuse fashion unrelated to tumor size or location.

Human papillomavirus in normal conjunctival tissue and in conjunctival papilloma: types and frequencies in a large series.

AIM: To examine conjunctival papilloma and normal conjunctival tissue for the presence of human papillomavirus (HPV). METHODS: Archival paraffin wax-embedded tissue from 165 conjunctival papillomas and from 20 histological normal conjunctival biopsy specimens was analysed for the presence of HPV by PCR. Specimens considered HPV positive using consensus primers, but with a negative or uncertain PCR result using type-specific HPV probes, were analysed with DNA sequencing. RESULTS: HPV was present in 86 of 106 (81%) beta-globin-positive papillomas. HPV type 6 was positive in 80 cases, HPV type 11 was identified in 5 cases and HPV type 45 was present in a single papilloma. All the 20 normal conjunctival biopsy specimens were beta-globin positive and HPV negative. CONCLUSION: There is a strong association between HPV and conjunctival papilloma. The study presents the largest material of conjunctival papilloma investigated for HPV and the first investigation of HPV in normal conjunctival tissue. HPV types 6 and 11 are the most common HPV types in conjunctival papilloma. This also is the first report of HPV type 45 in conjunctival papilloma.

Human papillomavirus and pterygium. Is the virus a risk factor?

BACKGROUND: Pterygium is a disease of unknown origin and pathogenesis that might be vision threatening. It is characterised by a wing-like conjunctival overgrowth of the cornea. Several studies have investigated human papillomavirus (HPV) as a risk factor for the development of pterygia, but the results are inconclusive. AIM: To investigate a large sample of pterygia for the presence of HPV in order to clarify the putative association between pterygia and HPV. METHODS: 100 specimens of pterygium from Danish patients and 20 normal conjunctival biopsy specimens were investigated for the presence of HPV with PCR technique using beta-globin primers to access the quality of the extracted DNA and the HPV primers MY09/11 and GP5+/6+. HPV-positive specimens underwent subsequent HPV typing with type-specific HPV primers and further investigation with DNA in situ hybridisation (ISH). RESULTS: 90 of 100 investigated pterygia proved suitable for HPV analysis by PCR. As beta-globin could not be amplified, 10 specimens were excluded from the study. 4 of 90 pterygia harboured HPV. HPV type 6 was identified in all four HPV-positive pterygia. The 20 normal conjunctival biopsy specimens were beta-globin positive and HPV negative. All four pterygia that were HPV type 6 positive were DNA ISH negative. CONCLUSIONS: The low presence of HPV DNA in pterygia does not support the hypothesis that HPV is involved in the development of pterygia in Denmark.

Bilateral diffuse uveal melanocytic proliferation: Case report and literature review.

Bilateral diffuse uveal melanocytic proliferation (BDUMP) is a rare paraneoplastic intraocular disease that causes progressive visual loss in patients driven by an IgG factor associated with an underlying malignancy. Characteristic ocular findings include exudative retinal detachment, rapid cataract formation and uveal melanocytic tumours. The awareness and documentation of BDUMP has increased during the past decade, and the increasing amount of data collected demonstrates the effect of treatment with plasmapheresis and the value of diagnostic tools in BDUMP such as genetic and immunologic investigations. The literature of BDUMP has not been reviewed since 2003, and there is a growing need for an updated review on diagnosis and management of BDUMP. We review the literature and report a case of BDUMP with a white ciliary body tumour, iris rubeosis, increased iris pigmentation and cataract.

Optic nerve invasion of uveal melanoma: clinical characteristics and metastatic pattern.

PURPOSE: To determine the frequency of optic nerve invasion in uveal melanoma, to identify clinical factors associated with optic nerve invasion, and to analyze the metastatic pattern and the association with survival. METHODS: All iris, ciliary body, and choroidal melanomas (N = 2758) examined between 1942 and 2001 at the Eye Pathology Institute, University of Copenhagen, Denmark, and the Institute of Pathology, Aarhus University Hospital, Aarhus, Denmark, were reviewed. Cases with optic nerve invasion were identified and subdivided into prelaminar or laminar invasion and postlaminar invasion. Clinical characteristics were compared with those from 85 cases randomly drawn from all ciliary body and choroidal melanomas without optic nerve invasion from the same period. Survival data were obtained by the Kaplan-Meier method, and the Mantel-Cox log-rank test was used to test differences in survival among the three patient groups. RESULTS: Optic nerve invasion was found in 157 uveal melanomas (5.7%; 95% confidence interval [CI], 4.8%-6.6%). Frequency varied during the observation period between 5% and 7%. Only choroidal and ciliary body melanomas were found to invade the optic nerve. Eighty-five (54%) were confined to the prelaminar or laminar part, and 72 (46%) were confined to the postlaminar part. Increased intraocular pressure (IOP) and juxtapapillary location were associated with prelaminar or laminar invasion and postlaminar invasion. Age older than 70 years, reduced vision to light perception or worse, nonvisible fundus, and large (>15 mm) tumor size were associated with postlaminar spread. In univariate analysis, patients with postlaminar invasion had significantly higher all-cause and melanoma-related mortality than the other patients. CONCLUSIONS: Optic nerve invasion in uveal melanoma is found in 1 in 20 patients. Visible juxtapapillary melanoma or loss of light perception should make the clinician suspicious of melanoma with optic nerve invasion, and special awareness of postlaminar spread should be addressed when increased IOP is present independently of decreased visual acuity and tumor location.

Morphological features in eyes with endophthalmitis after cataract surgery - histopathology and optical coherence tomography assessment.

PURPOSE: To assess the ocular damage that occurs in eyes with postoperative endophthalmitis after cataract surgery (PE) based on optical coherence tomography (OCT) retinal scans of PE eyes and histological specimens of eyes removed due to PE. METHODS: Case-control study and case series. Fifty-one patients who had previously developed PE were clinically examined with OCT scans of the retina of both eyes. Histological specimens of 10 removed PE eyes were studied. RESULTS: The OCT scans showed that PE eyes had a statistically significantly higher frequency of hyperdense elements on the internal limiting membrane (ILM) of the retina (14 eyes versus 3 eyes, p = 0.015) and a higher degree of retinal atrophy temporal to the fovea (13 eyes versus 1 eye, p = 0.013) compared to fellow eyes. The histopathological analyses showed the formation of epiretinal membranes, derangement of all retinal layers with a reduced number of nuclei in the nuclear layers, loss of photoreceptor outer segments and massive retinal gliosis. CONCLUSIONS: Optical coherence tomography scans of the retina and histopathology analyses provide insights in the pathological process occurring in PE.

Primary basal cell carcinoma of the caruncle with seeding to the conjunctiva.

BACKGROUND: To report the clinical and histopathological characteristics of a patient with a primary basal cell carcinoma (BCC) of the caruncle with seeding of the tumour to the conjunctiva. METHODS: Surgical excision and histological examination. RESULTS: A 60-year-old female presented with a lesion of the caruncle. Clinical examination revealed a pale lobulated tumour without skin involvement. Computer tomography scans showed orbital invasion. The tumour was excised. Three years later a small polypoid tumour developed in the inferior fornix of the same eye. Two and a half years later, the patient developed an orbital recurrence. Microscopically, both neoplasms were composed of infiltrative islands of basaloid tumour cells, scattered mitoses and peripheral palisading consistent with the diagnosis of BCC. CONCLUSION: This case describes a primary BCC of the caruncle with seeding to the conjunctiva.

Long term follow-up of persistent choroidal folds and hyperopic shift after complete removal of a retrobulbar mass.

BACKGROUND: Hyperopic shift and chorioretinal folds are common findings with intraorbital masses compressing the posterior pole of the globe. These signs usually regress after complete tumour excision. To the best of our knowledge this is the first reported case, where optical coherence tomography was used to document persistent chorioretinal folds after complete excision of a retrobulbar mass. CASE PRESENTATION: A 47-year-old Caucasian woman was referred to our department with long-documented hyperopic shift and gradually decreasing vision in her left eye. Optical coherence tomography showed chorioretinal folds. Magnetic resonance imaging revealed a retrobulbar mass which caused flattening of the posterior pole of the globe. The tumour was successfully removed, and was confirmed to be a cavernous haemangioma on histological assessment. 3 years after surgery the patient still has a similar amount of hyperopia and chorioretinal folds. CONCLUSION: Choroidal folds and hyperopic shift may persist after complete tumour removal. Long term follow-up is advised to rule out recurrence of the intraorbital mass.

Squamous cell dysplasia and carcinoma of the conjunctiva. A nationwide, retrospective, epidemiological study of Danish patients.

PURPOSE: To investigate the epidemiology of squamous cell dysplasia and carcinoma of the conjunctiva in Denmark. METHODS: Review of the histopathological case reports at the Eye Pathology Institute (EPI), University of Copenhagen, and the National Danish Pathology Bank from 1980 to 2011. Information regarding distribution of age and sex, localization, earlier pathology, comorbidity and recurrence of the condition was registered. The Cause of Death Registry at Statens Serum Institut was used to obtain information regarding cause of death. RESULTS: A total of 143 cases were identified. Ninety-five (61%) had epithelial dysplasia, 19 (13%) had carcinoma in situ, and 29 (20%) had squamous cell carcinoma. A significantly higher proportion of men were found. The median age at diagnosis was 65 years. The risk of recurrence was 10.0% [95% confidence interval (CI): 5.0-15.0] after 1 year and 17.2% (95% CI: 10.8-23.7) after 5 years. The lesions were most often localized to the corneal limbus. In our records, one patient had a lymph node metastasis and the disease necessitated enucleation in two patients. No patients had died from squamous cell carcinoma of the conjunctiva. CONCLUSION: Overall, our data are in agreement with the results of previous studies in Northern, high-latitude countries. There is a low incidence rate; the lesions are predominantly seen in men in their seventh decade and localized to the corneal limbus. The risk of recurrence is high, and the benign lesions have potential to progress to frank carcinoma.