Periocular Sebaceous Carcinoma: A Case Audit from the National Specialist Ophthalmic Pathology Service in Liverpool from 2009 to 2022 to Assess the Diagnostic Utility of PRAME Expression.

Introduction: Periocular sebaceous carcinoma (PSC) remains a common diagnostic pitfall both clinically and histomorphologically. PRAME (preferentially expressed antigen in melanoma) has been studied in the various neoplasms as proposed as diagnostic and therapeutic markers. PRAME is expressed in normal sebaceous units and in some sebaceous lesions; however, its utility in sebaceous carcinoma diagnosis has not yet been extensively investigated. We conducted a 13-year retrospective review of the patients diagnosed with PSC at the National Specialist Ophthalmic Pathology Service in Liverpool. Herein, we report the histomorphological and immunohistochemical (IHC) features of these tumors, particularly PRAME expression in this cohort. Methods: Thirty-one PSC cases diagnosed between 2009 and 2022 were retrieved from the histopathology archives. Twenty cases diagnosed as invasive PSC and 11 cases with in situ PSC were included. The hematoxylin and eosin (H&E) slides and previously performed IHC slides were reviewed; clinical information data were obtained. Cases with an adequate tissue were also stained for PRAME (preferentially expressed antigen in melanoma) and adipophilin (if not already performed). Results: In total, there were 24 females and 7 males diagnosed with PSC, ranging from 55 to 90 years (median, 78 years). The types of specimens received were 11 conjunctival mapping biopsies, 19 excisions/wedge resections, and 1 orbital exenteration. The eyelid was the commonest site involved (n = 24), followed by eyelid with conjunctiva (3), and conjunctiva alone (4). All patients presented with the clinical suspicion of malignancy. Histologically, 11 invasive PSC (55%) exhibited poorly differentiated morphology, composed of predominantly atypical basaloid cells with minimal sebocytic differentiation; 9 cases (45%) were moderately differentiated with noticeable finely multivacuolated cytoplasm; and 3 (15%) showed associated comedo necrosis. Most invasive PSC showed moderate-to-brisk mitotic activities. Of those cases with available immunostains (n = 31), 25 (80.6%) expressed adipophilin; 18 (58.1%) Ber-EP4; 14 (45.2%) epithelial membrane antigen (EMA); and 5 (16.1%) both androgen receptor and perforin positivity. PRAME expression was seen in normal sebaceous glands; however, only (5/19; 26%) of invasive PSC showed focal weak-to-moderate PRAME positivity, and mostly in moderately differentiated tumors. None of the in situ PSCs were PRAME-positive. Conclusions: Most PSCs are moderate-to-poorly differentiated. Although PRAME is expressed in normal sebaceous units, it appears less useful as diagnostic marker for PSC, especially in poorly differentiated tumors. In difficult cases, panels of IHC studies (adipophilin, Ber-EP4, and EMA) achieve a definitive diagnosis.

A Multicenter Study Validates the WHO 2022 Classification for Conjunctival Melanocytic Intraepithelial Lesions With Clinical and Prognostic Relevance.

Several nomenclature and grading systems have been proposed for conjunctival melanocytic intraepithelial lesions (C-MIL). The fourth "WHO Classification of Eye Tumors" (WHO-EYE04) proposed a C-MIL classification, capturing the progression of noninvasive neoplastic melanocytes from low- to high-grade lesions, onto melanoma in situ (MIS), and then to invasive melanoma. This proposal was revised to the WHO-EYE05 C-MIL system, which simplified the high-grade C-MIL, whereby MIS was subsumed into high-grade C-MIL. Our aim was to validate the WHO-EYE05 C-MIL system using digitized images of C-MIL, stained with hematoxylin and eosin and immunohistochemistry. However, C-MIL cases were retrieved from 3 supraregional ocular pathology centers. Adequate conjunctival biopsies were stained with hematoxylin and eosin, Melan-A, SOX10, and PReferentially expressed Antigen in Melanoma. Digitized slides were uploaded on the SmartZoom platform and independently scored by 4 ocular pathologists to obtain a consensus score, before circulating to 14 expert eye pathologists for independent scoring. In total, 105 cases from 97 patients were evaluated. The initial consensus diagnoses using the WHO-EYE04 C-MIL system were as follows: 28 benign conjunctival melanoses, 13 low-grade C-MIL, 37 high-grade C-MIL, and 27 conjunctival MIS. Using this system resulted in 93% of the pathologists showing only fair-to-moderate agreement (kappa statistic) with the consensus score. The WHO-EYE05 C-MIL system (with high-grade C-MIL and MIS combined) improved consistency between pathologists, with the greatest level of agreement being seen with benign melanosis (74.5%) and high-grade C-MIL (85.4%). Lowest agreements remained between pathologists for low-grade C-MIL (38.7%). Regarding WHO-EYE05 C-MIL scoring and clinical outcomes, local recurrences of noninvasive lesions developed in 8% and 34% of the low- and high-grade cases. Invasive melanoma only occurred in 47% of the cases that were assessed as high-grade C-MIL. This extensive international collaborative study is the first to undertake a comprehensive review of the WHO-EYE05 C-MIL scoring system, which showed good interobserver agreement and reproducibility.

Tumor-Associated Retinal Pigmentation in Choroidal Melanoma.

PURPOSE: To report a previously unrecognized choroidal melanoma clinical feature termed tumor-associated retinal pigmentation (TARP) and determine any correlation with tumor biology. DESIGN: Imaging and histologic analysis of a retrospective cohort of patients. PARTICIPANTS: Patients with choroidal melanoma identified as having TARP on funduscopy at the Liverpool Ocular Oncology Centre (LOOC), United Kingdom, from January 2020 through January 2023. METHODS: Clinical and imaging characteristics of patients diagnosed with choroidal melanoma and exhibiting TARP on fundoscopy were documented. Details of these choroidal melanomas were collated and correlated with histopathology and molecular genetic reports. The chromosome 3 status of each tumor was assessed. In enucleated samples, immunostaining was undertaken to determine the nature of the TARP using specific markers (CD68 and MelanA). MAIN OUTCOME MEASURES: Features of TARP on widefield fundus color imaging, fundus autofluorescence (FAF), and OCT were described. Tumor chromosome 3 status and the immunoprofile of the TARP also were collated. RESULTS: Tumor-associated retinal pigmentation had a prevalence rate of 7.47 per 100 cases of choroidal melanoma at the LOOC. Twenty-three eyes with TARP were analyzed, with a mean age of 71.4 years (range, 51-88 years). The median largest basal diameter was 16.10 mm (range, 9.17-21.32 mm), and the mean tumor thickness was 8.04 mm (range, 1.40-13.80 mm). Tumor-associated retinal pigmentation was observed on widefield color fundus imaging, with hypofluorescence on FAF images and represented hyperreflective foci located in intraretinal and subretinal spaces on OCT scans. Seventeen patients (73.9%) underwent enucleation, and 6 patients (26.1%) underwent globe-sparing treatment. Molecular genetic analysis of 20 choroidal melanomas (after enucleation or radiotherapy biopsy) revealed monosomy 3 in 18 tumors (90%). Immunostaining of the TARP in enucleated eyes showed CD68+ melanophages in all 17 patients appearing as scattered cells and aggregates; MelanA findings were negative. CONCLUSIONS: Tumor-associated retinal pigmentation represents tumor-associated macrophages, not melanocytes, within intraretinal and subretinal spaces of larger choroidal melanomas. Radiation treatments need not involve this area in the treatment plan, minimizing radiation-related complications. This novel clinical sign seems to be linked to tumors of high metastatic-risk clinical and genetic characteristics, with a preponderance having monosomy 3 anomalies. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Low-Dose Propofol with Peribulbar Anaesthesia for Cataract Surgery.

In this paper, we investigate the effect of sedation using low-dose propofol on patient reported outcome measures (PROMS) in patients undergoing cataract surgery. This is a randomised, single-blinded observational prospective study. Patients undergoing elective cataract surgery using peribulbar anaesthesia over consecutive cataract lists were selected for this trial. Patients were randomised to receive either no sedation or low-dose propofol (20 to 30 mg followed by 10 mg increments until the patient developed slurred speech alone) prior to the administration of local anaesthesia. Pain, satisfaction, anxiety, needle recall, pulse, and blood pressure (BP) were measured. A total of 97 patients were included, 50 of whom received propofol. There were 4 senior surgeons and anaesthetists. There were no ocular or systemic complications and all patients had uncomplicated surgery. Anxiety (p = 0.026), needle recall (p < 0.001), difference in systolic BP (p = 0.043), and pulse (p = 0.046) were dependent on patient age (p < 0.001) and the use of propofol (p = 0.007). Lower pain was associated with propofol (p = 0.008), as well as lower anxiety (p = 0.002), and increased patient age (p = 0.014). The administration of propofol was significantly associated with lower needle recall (p < 0.001), pre- to post-operative difference in systolic BP (p = 0.029), and mean BP (p = 0.044). Low-dose propofol given immediately prior to administration of local anaesthesia was associated with reduced pain and needle recall, as well as lower BP.

A Retrospective Analysis of 10 Years of Liver Surveillance Undertaken in Uveal Melanoma Patients Treated at the Supraregional "Liverpool Ocular Oncology Centre", UK.

PURPOSE: To determine liver screening frequency and modality in UM patients following primary treatment, and the characteristics of detected metastases. METHODS: A 10-year retrospective study of 615 UM patients undergoing liver surveillance in Liverpool. Information was collected from liver scan reports of these patients. RESULTS: Of 615 UM patients analyzed, there were 337 men (55%) and 278 women (45%). Median age at primary treatment was 61 years (range, 22-94). At study end, median follow-up was 5.1 years, with 375 patients (61%) alive and 240 deceased (39%). Of the deceased patients, 187 (78%) died due to metastatic UM; 24 (10%) deaths were due to other causes; and 29 (12%) patients died of unknown conditions. In total, 3854 liver scans were performed in the 615 UM patients, with a median of 6.2 scans per patient (range, 1-40). Liver MRI was most frequently performed (62.8%). In total, 229 (37%) UM patients developed metastases during the study period: 150 were detected via liver surveillance and 79 were observed post-mortem. CONCLUSIONS: Metastatic UM onset is related to the size and genetic profiles of the primary UM, and can be predicted using the model LUMPO3. Regular liver surveillance allowed for timely detection of metastases, and through metastasectomy can lead to prolongation of life in some patients.

Optic nerve head sarcoidosis mimicking an intraocular tumour, and occurring as the first manifestation of neuro-ocular sarcoidosis.

PURPOSE: Sarcoidosis is a chronic idiopathic granulomatous inflammatory disease that can affect many major organ systems, primarily the lungs, and hence has remarkable clinical heterogeneity. At least 50% of patients with systemic sarcoidosis develop inflammatory eye disease, and in approximately 21% of cases, it may be the first clinical manifestation. Neuro-ocular involvement occurs in <3% of all sarcoidosis cases, and rarely involves the optic nerve. We describe an unusual case of an intraocular sarcoidosis presenting as an unclear optic nerve mass. OBSERVATIONS: A 61-year-old male presented with painful gradual visual loss in the right eye. Previous history included Stage II Hodgkin lymphoma (HL) and concurrent mediastinal sarcoidosis, both in remission 5 years later. On examination, the right eye (RE) vision had no light perception, neovascular glaucoma, attenuated retinal vessels and a non-pigmented optic disc mass. The left eye was normal. The RE showed no response to oral steroids, was painful due to neovascular glaucoma and the concerns of recurrent HL with intraocular manifestations lead to RE enucleation. Macroscopic examination revealed a whitish mass at the optic disc, which histomorphologically showed a non-necrotising granulomatous inflammation consuming the optic nerve head and extending into the optic nerve resection margin. Special stains for microorganisms were negative. The uveal tract was free of inflammation. The morphological features were consistent with optic nerve sarcoidosis. A diagnosis of neuro-ocular sarcoidosis was made, and the patient was commenced on infliximab. CONCLUSION: Neuro-ocular sarcoidosis is known as the 'great imitator' because it can cause a variety of non-specific clinical signs and symptoms, mimicking many other conditions, including lymphomas. Intraocular sarcoidosis is not unusual and typically affects the uvea. Isolated optic nerve sarcoidosis is rare. The challenging aspect of intraocular sarcoidosis is the requirement of prompt treatment to reverse any eye damage and prevent permanent visual loss. Here, optic nerve sarcoidosis was very advanced, and was associated with intracerebral manifestations. IMPORTANCE: Neuro-ocular sarcoidosis is a difficult condition to diagnose and treat. Our case was complicated by the previous history of HL and concurrent mediastinal sarcoidosis which were in remission. In patients with a history of sarcoidosis with new loss of vision and neurological weaknesses oculocerebral involvement must be included in the differential diagnosis even in the absence of typical manifestations of ocular sarcoidosis as in uveal tract involvement.

Transcriptome Profiling Reveals New Insights into the Immune Microenvironment and Upregulation of Novel Biomarkers in Metastatic Uveal Melanoma.

Metastatic uveal melanoma (mUM) to the liver is incurable. Transcriptome profiling of 40 formalin-fixed paraffin-embedded mUM liver resections and 6 control liver specimens was undertaken. mUMs were assessed for morphology, nuclear BAP1 (nBAP1) expression, and their tumour microenvironments (TME) using an "immunoscore" (absent/altered/high) for tumour-infiltrating lymphocytes (TILs) and macrophages (TAMs). Transcriptomes were compared between mUM and control liver; intersegmental and intratumoural analyses were also undertaken. Most mUM were epithelioid cell-type (75%), amelanotic (55%), and nBAP1-ve (70%). They had intermediate (68%) or absent (15%) immunoscores for TILs and intermediate (53%) or high (45%) immunoscores for TAMs. M2-TAMs were dominant in the mUM-TME, with upregulated expression of ANXA1, CD74, CXCR4, MIF, STAT3, PLA2G6, and TGFB1. Compared to control liver, mUM showed significant (p < 0.01) upregulation of 10 genes: DUSP4, PRAME, CD44, IRF4/MUM1, BCL2, CD146/MCAM/MUC18, IGF1R, PNMA1, MFGE8/lactadherin, and LGALS3/Galectin-3. Protein expression of DUSP4, CD44, IRF4, BCL-2, CD146, and IGF1R was validated in all mUMs, whereas protein expression of PRAME was validated in 10% cases; LGALS3 stained TAMs, and MFGEF8 highlighted bile ducts only. Intersegmental mUMs show differing transcriptomes, whereas those within a single mUM were similar. Our results show that M2-TAMs dominate mUM-TME with upregulation of genes contributing to immunosuppression. mUM significantly overexpress genes with targetable signalling pathways, and yet these may differ between intersegmental lesions.

Patterns of BAP1 protein expression provide insights into prognostic significance and the biology of uveal melanoma.

Uveal melanoma (UM) is a rare aggressive intraocular tumour with a propensity for liver metastases, occurring in ∼50% of patients. The tumour suppressor BAP1 is considered to be key in UM progression. Herein, we present the largest study to date investigating cellular expression patterns of BAP1 protein in 165 UMs, correlating these patterns to prognosis. Full clinical, histological, genetic, and follow-up data were available for all patients. BAP1 gene sequencing was performed on a subset of 26 cases. An independent cohort of 14 UMs was examined for comparison. Loss of nuclear BAP1 (nBAP1) protein expression was observed in 54% (88/165) UMs. nBAP1 expression proved to be a significant independent prognostic parameter: it identified two subgroups within monosomy 3 (M3) UM, which are known to have a high risk of metastasis. Strikingly, nBAP1-positiveM3 UMs were associated with prolonged survival compared to nBAP1-negative M3 UMs (Log rank, p = 0.014). nBAP1 protein loss did not correlate with a BAP1 mutation in 23% (6/26) of the UMs analysed. Cytoplasmic BAP1 protein (cBAP1) expression was also observed in UM: although appearing 'predominantly diffuse' in most nBAP1-negative UM, a distinct 'focal perinuclear' expression pattern - localized immediately adjacent to the cis Golgi - was seen in 31% (18/59). These tumours tended to carry loss-of-function BAP1 mutations. Our study demonstrates loss of nBAP1 expression to be the strongest prognostic marker in UM, confirming its importance in UM progression. Our data suggest that non-genetic mechanisms account for nBAP1 loss in a small number of UMs. In addition, we describe a subset of nBAP1-negative UM, in which BAP1 is sequestered in perinuclear bodies, most likely within Golgi, warranting further mechanistic investigation.

Chronic Lymphocytic Leukaemia/ Small-Cell Lymphocytic Lymphoma of the Lacrimal Sac: A Case Series.

BACKGROUND: Lymphomas of the lacrimal sac are rare, accounting for less than 10% of lacrimal sac malignant tumours. They may present with symptoms typical of secondary acquired nasolacrimal duct obstruction and are thus often misdiagnosed. METHODS: Case series and literature review. RESULTS: Herein we describe 3 cases of chronic lymphocytic leukaemia (CLL)/small-cell lymphocytic lymphoma (SLL) of the lacrimal sac with immunohistochemical and in 1 case molecular confirmation. CONCLUSION: Lymphomas of the lacrimal sac should be suspected in patients with known CLL presenting with epiphora and dacryocystitis. During dacryocystorhinostomy, an incisional biopsy of the lacrimal sac is essential for confirming CLL/SLL involvement and may guide treatment.

Inflammatory cell infiltrates in advanced metastatic uveal melanoma.

Current treatments for metastatic uveal melanoma (mUM) are limited and rarely prolong patient survival. Immunotherapy trials for mUM are few and to date have demonstrated only marginal success. High densities of tumor-associated macrophages (TAMs) and infiltrating T lymphocytes (TILs) in primary UM are associated with poor prognosis. Little is known about the immune microenvironment of mUM. Our aim was to examine the presence and distribution of TAMs and TILs in mUM within the liver. Whole-tissue sections of liver mUM (n=35) were examined by immunohistochemistry. For TAMs, monoclonal antibodies against CD68 and CD163 were used. Macrophage density and morphology were scored using previous established systems. Density and spatial distribution of TILs were highlighted using antibodies against CD3 (pan-lymphocyte marker), CD4 (T-helper cells), and CD8 (T-cytotoxic cells). CD68+ and CD163+ TAMs were seen within the tumor in all 35 specimens; their density was "moderate" in 50% of cases and "few" in 43%, and the majority showed an "indeterminate" phenotype. CD3+ TILs were noted both within mUMs and surrounding the tumor. Of these, CD8+ TILs were "few" in number within mUM but were predominantly seen peritumorally at the tumor/normal liver interface, whereas CD4+ TILs showed a high perivascular density within mUM. CD68+ and CD163+ TAMs of "indeterminate" morphology were observed in mUM, suggesting a tendency toward the protumorigenic M2 phenotype. CD4+ TILs were seen within the mUM, whereas CD8+ TILs tended to be peritumoral. The biological and functional roles of inflammatory cells in mUM require further investigation to determine if they represent potential targets for future therapies in mUM.

Lacrimal Sac Tumors--A Review.

Tumors of the lacrimal sac are rare but their recognition and early management are imperative, as they are locally invasive and potentially life-threatening. Because of their rarity, large clinical studies with statistically significant data on the natural course, management, and prognosis of these neoplasms are unavailable. Current practices are therefore based on a few case series and a small number of isolated case reports. Most tumors are primary and of epithelial origin (60-94%), of which 55% are malignant. Lacrimal sac tumors typically present with epiphora and a palpable mass over the medial canthus and are thus often erroneously diagnosed as chronic dacryocystitis. A full history with clinical and diagnostic workup is essential to plan treatment, which is often multi-disciplinary. Statistically significant associations have been shown with higher tumor staging and size with increased metastatic risk and lower survival rates. Management usually involves complete surgical resection with adjuvant radiotherapy and/or chemotherapy for malignant lesions. Long-term follow-up is required, as recurrences and metastases can occur many years after initial treatment.

Genetic findings in treatment-naïve and proton-beam-radiated iris melanomas.

BACKGROUND/AIMS: Iris melanomas (IM) are rare and have a lower mortality than posterior uveal melanomas (UM). Our aims were to determine the prevalence of genetic changes associated with prognosis of posterior UM, in both treated and non-treated IM. METHODS: Retrospective database review and molecular analysis of all patients diagnosed with IM at the Liverpool Ocular Oncology Centre (LOOC) between 1993 and 2015. Archival pathology specimens of confirmed IM cases were analysed for chromosomal alterations, using multiplex ligation-dependent probe amplification (MLPA) or microsatellite analysis (MSA) depending on DNA yield, and BRAF mutation status. RESULTS: 5189 patients were diagnosed with intraocular melanoma at LOOC from 1993 to 2015. Of these, 303 (5.8%) patients were diagnosed with IM. Tissue samples were available for 26 IM cases. Twelve of these cases had biopsies taken post-proton beam radiotherapy (PBR). Histological subtyping showed 14 IM being spindle, 2 epithelioid and 10 were of mixed cell type. Twenty of the 26 IM cases (77%) analysed genetically were classified as either disomy 3 (n=16) or monosomy 3 (n=4). Chromosome 6p gain was detected in 4/18 (22%) IM, and polysomy 8q in 6%. BRAF mutations were not detected in any of the four IM cases examined. One patient with IM died from metastatic disease: this tumour was disomy 3 with 6p and 8q gains. All other patients were alive with no evidence of metastases at study closure. CONCLUSIONS: Chromosomal aberrations seen in posterior UM can also be demonstrated using MLPA or MSA in both treatment naïve and PBR-treated IM. Most IM display a low-metastatic risk chromosomal profile.

Transplant rejection following endothelial keratoplasty and penetrating keratoplasty in the United Kingdom: incidence and survival.

PURPOSE: To investigate the incidence and outcome of cornea transplant rejection following endothelial keratoplasty (EK) and penetrating keratoplasty (PK) for Fuchs endothelial dystrophy (FED) and pseudophakic bullous keratopathy (PBK). DESIGN: Multicenter cohort study. METHODS: Patients registered on the United Kingdom Transplant Registry (UKTR) who had an EK or PK for FED or PBK between April 1, 2005 and March 31, 2011 were included. Data were collected from UKTR forms at 1 and 2 years. Postoperative steroid use varies between surgeons and cannot be captured in this reporting system. Rejection events were identified as those recorded as endothelial rejection. RESULTS: A total of 3486 corneal transplants were undertaken: 1973 for FED, 1513 for PBK. For FED, 2-year rejection-free survival was 93% (95% confidence interval [CI] 90%-94%) for PK and 94% (95% CI 92%-96%) for EK (P = .3). In transplants that had a rejection episode, 50% of PKs (17) and 60% of EKs (15) subsequently failed. For PBK, 2-year rejection-free survival for PK was 88% (95% CI 86%-90%) and 90% (95% CI 86%-92%) for EK (P = .6). In transplants that had a rejection episode, 85% of PKs (41) and 76% of EKs (22) subsequently failed. Inflammation (ie, conjunctival injection, presence of keratic precipitates and intraocular signs) at the time of surgery for patients with FED was significant for developing rejection: 3.5 times greater compared with those with no inflammation (P = .02). CONCLUSIONS: There is no significant difference in rejection-free survival between EK and PK for FED or PBK. The presence of inflammation is an important risk factor, and attention to its control before and following surgery is important.

Novel heavy tamponade for vitreoretinal surgery.

PURPOSE: The aim of this study was to produce a heavy tamponade with a specific gravity greater than 1.06 g/mL that was optically transparent, could be manufactured using simple processing, could be injected using standard clinical equipment, and would have appropriate biocompatibility. METHODS: Aerosil silica was added to a phenyl trimethicone and mixed via a roller, overhead stirring, and ultrasonics. The refractive index, visible absorbance, and shear viscosity were measured. The injectability of the solutions was evaluated using the Accurus Viscous Fluid Injection system. The tamponade efficiency was assessed using a model eye chamber and compared with that of Densiron 68, Oxane HD, and F6H8. The biocompatibility was evaluated in vitro and in vivo in rabbits. RESULTS: Tamponade agents were produced with specific gravities of 1.10, 1.11, 1.13, and 1.16 g/mL that had good optical clarity. Mixing using overhead stirring was sufficient to produce tamponade agents with shear viscosities in the range 1000 to 5000 mPa·s that were reproducible and stable during storage. The solutions were easier to inject using the Accurus Viscous Fluid Injection system than silicone oil 1000 mPa·s. The 11% silica solution had greater tamponade efficiency than Densiron 68 or Oxane HD. There was no evidence of cytotoxicity in vitro. Silica solution 11% induced cataract earlier than Polydimethylsiloxane 1000 (PDMS 1000). Silica solution 11% and phenyl trimethicone reduced the a-wave value at 1 week after vitrectomy, but recovery was observed at later time points. Silica solution 11% caused inner nuclear layer (INL) nuclei dropdown in inferior retina from 4 weeks postoperation. Polydimethylsiloxane 1000 induced a similar phenomenon in superior retina 12 weeks postoperation. CONCLUSIONS: We have produced a heavy tamponade with good clarity that has appropriate shear viscosity, injectibility, enhanced tamponade efficiency, and biocompatibility similar to that of PDMS 1000.

Plasma polymer coatings to aid retinal pigment epithelial growth for transplantation in the treatment of age related macular degeneration.

Subretinal transplantation of functioning retinal pigment epithelial (RPE) cells grown on a synthetic substrate is a potential treatment for age-related macular degeneration (AMD), a common cause of irreversible vision loss in developed countries. Plasma polymers give the opportunity to tailor the surface chemistry of the artificial substrate whilst maintaining the bulk properties. In this study, plasma polymers with different functionalities were investigated in terms of their effect on RPE attachment and growth. Plasma polymers of acrylic acid (AC), allyl amine (AM) and allyl alcohol (AL) were fabricated and characterised using X-ray photoelectron spectroscopy (XPS) and water contact angle measurements. Octadiene (OD) hydrocarbon films and tissue culture polystyrene were used as controls. Wettability varied from hydrophobic OD to relatively hydrophilic AC. XPS demonstrated four very different surfaces with the expected functionalities. Attachment, proliferation and morphological examination of an RPE cell line and primary RPE cells were investigated. Both cell types grew on all surfaces, with the exception of OD, although the proliferation rate of primary cells was low. Good epithelial morphology was also demonstrated. Plasma polymerised films show potential as cell carrier surfaces for RPE cells in the treatment of AMD.

Polydimethylsiloxane as a substrate for retinal pigment epithelial cell growth.

Retinal pigment epithelial (RPE) cell transplantation represents potential treatment for age-related macular degeneration (AMD). Because delivery of isolated cells can cause serious complications, it is necessary to develop a suitable transplant membrane that could support an intact functioning RPE monolayer. Polydimethylsiloxane (PDMS) possesses the physical properties required for a transplanting device and is widely used clinically. We have investigated the use of PDMS as a potential surface for the growth of healthy RPE monolayers. PDMS discs were surface modified by air and ammonia gas plasma treatments. Dynamic contact angles were measured to determine the changes in wettability. Human ARPE-19 cells were seeded onto untreated and treated samples. Cell number, morphology and monolayer formation, cytotoxicity, and phagocytosis of photoreceptor outer segments (POS) were assessed at set time-points. Air plasma treatment increased the wettability of PDMS. This significantly enhanced cell growth, reaching confluence by day 7. Immunofluorescence revealed well-defined actin staining, monolayer formation, and high cell viability on air plasma treated and untreated surfaces, and to a lesser extent, on ammonia plasma treated. Furthermore, RPE monolayers were able to demonstrate phagocytosis of POS in a time-dependent manner similar to control. PDMS can support an intact functional monolayer of healthy differentiated RPE cells.