AUSTRALIAN AND NEW ZEALAND STUDY OF PHOTODYNAMIC THERAPY IN CHOROIDAL AMELANOTIC MELANOMA.

PURPOSE: To evaluate the safety and efficacy of primary photodynamic therapy (PDT) for posterior choroidal amelanotic melanomas. METHODS: Patients with posterior choroidal amelanotic melanomas up to 6 mm in height were treated with PDT using verteporfin as the photosensitizing agent. Treatment was repeated every 3 months until the tumor was flat up to a maximum of 6 treatments. Tumor response and recurrence was assessed by clinical examination, photography, and ultrasonography. Patients were monitored 3 monthly for a minimum of 3 years. RESULTS: Thirty-six of 41 (88%) patients had complete regression after an initial course of PDT. Of them, 20 (56%) had no recurrence, 3 (8%) had recurrences that were successfully treated with further PDT, and 13 (36%) had recurrences that failed or were not amenable to further PDT. None of the measured baseline characteristics predicted treatment outcomes. There was no reduction in visual acuity due to PDT. The mean follow-up time was 3.5 years. CONCLUSION: In this large series, primary PDT was highly effective in achieving initial regression of posterior choroidal amelanotic melanomas. Photodynamic therapy is a vision-preserving treatment option for these tumors; however, patients need to be followed up closely because there is a significant rate of recurrence.

PAX6 molecular analysis and genotype-phenotype correlations in families with aniridia from Australasia and Southeast Asia.

Purpose: Aniridia is a congenital disorder caused by variants in the PAX6 gene. In this study, we assessed the involvement of PAX6 in patients with aniridia from Australasia and Southeast Asia. Methods: Twenty-nine individuals with aniridia from 18 families originating from Australia, New Caledonia, Cambodia, Sri Lanka, and Bhutan were included. The PAX6 gene was investigated for sequence variants and analyzed for deletions with multiplex ligation-dependent probe amplification. Results: We identified 11 sequence variants and six chromosomal deletions, including one in mosaic. Four deleterious sequence variants were novel: p.(Pro81HisfsTer12), p.(Gln274Ter), p.(Ile29Thr), and p.(Met1?). Ocular complications were associated with a progressive loss of visual function as shown by a visual acuity ≤ 1.00 logMAR reported in 65% of eyes. The prevalence of keratopathy was statistically significantly higher in the Australasian cohort (78.6%) compared with the Southeast Asian cohort (9.1%, p=0.002). Variants resulting in protein truncating codons displayed limited genotype-phenotype correlations compared with other variants. Conclusions: PAX6 variants and deletions were identified in 94% of patients with aniridia from Australasia and Southeast Asia. This study is the first report of aniridia and variations in PAX6 in individuals from Cambodia, Sri Lanka, Bhutan, and New Caledonia, and the largest cohort from Australia.

Management of diffuse ocular surface squamous neoplasia: efficacy and complications of topical chemotherapy.

BACKGROUND: Ocular surface squamous neoplasia (OSSN) characterized by diffuse conjunctival or corneal spread is much less common than localized conjunctival disease. However, it is an important subcategory of the disease because of the difficulty it poses to treatment. It is rarely amenable to simple excision, and a purely surgical approach usually necessitates ocular surface reconstruction. Primary treatment with topical chemotherapy is an alternative, but its efficacy for these lesions is not well understood. DESIGN: Retrospective case series. PARTICIPANTS: Thirty-eight eyes treated for diffuse OSSN, defined as a lesion extending over five or more limbal clock hours or by extensive central or paracentral corneal spread. METHODS: Treatment utilized either topical 5-FU 1% or mitomycin-C (MMC) 0.04%. MAIN OUTCOME MEASURES: (i) Disease remission; (ii) complications. RESULTS: Thirty-two patients were treated for a primary diffuse OSSN. Ten patients (31%) required further treatment for disease persistence or recurrence. Thirteen patients had previously undergone a single unsuccessful treatment course for diffuse OSSN. Administration of a second treatment course (whether MMC or 5FU) was successful in 46% (six) of patients. 5-FU 1% resulted in drug-related complications in seven of 12 cases, and included a single case of focal paracentral corneal stromal melt. MMC 0.04% resulted in transient drug related complications in 23 of 39 cases. CONCLUSION: Diffuse OSSN is often recalcitrant to initial treatment with either 5-FU 1% or MMC 0.04%, and a pragmatic and vigilant approach to this heterogenous disease is required. Compared to localized disease, diffuse disease often requires multiple treatment efforts.

Long-term outcomes after adjunctive topical 5-flurouracil or mitomycin C for the treatment of surgically excised, localized ocular surface squamous neoplasia.

BACKGROUND: To report rates of recurrence and complications of localized ocular surface squamous neoplasia treated with 5-fluorouracil or mitomycin C as adjunctive treatment to surgical excision. DESIGN: Long-term follow up of two prospective, non-comparative interventional case series. PARTICIPANTS: One hundred fifty-three eyes with histologically confirmed localized, non-invasive ocular surface squamous neoplasia. 89 eyes were treated with adjuvant 5-fluorouracil and 64 eyes were treated with adjuvant mitomycin C. METHODS: Following surgical excision±cryotherapy patients received topical 5-fluorouracil 1% four times daily for two weeks or topical mitomycin C 0.04% four times daily for two to three 1-week cycles. MAIN OUTCOME MEASURES: Ocular surface squamous neoplasia recurrence, complications of therapy and compliance. RESULTS: Median follow up was 33.6 (range 12-84) months and 57.9 (range 12-160) months in 5-fluorouracil and mitomycin C groups, respectively. There was one recurrence in the 5-fluorouracil group and no recurrences in the mitomycin C group. Side-effects occurred in 69% of 5-fluorouracil patients and 41% of mitomycin C patients. Five patients (6%) required intervention for treatment-related side-effects in the 5-fluorouracil group versus 11 (17%) in the mitomycin C group. No vision-threatening complications were noted. CONCLUSIONS: Long-term recurrence of localised ocular surface squamous neoplasia is rare when topical 5-fluorouracil or mitomycin C are used as adjunctive treatment to surgical excision. While side-effects are common, the majority are transient and rarely limit compliance.

Homozygous mutations in PXDN cause congenital cataract, corneal opacity, and developmental glaucoma.

Anterior segment dysgenesis describes a group of heterogeneous developmental disorders that affect the anterior chamber of the eye and are associated with an increased risk of glaucoma. Here, we report homozygous mutations in peroxidasin (PXDN) in two consanguineous Pakistani families with congenital cataract-microcornea with mild to moderate corneal opacity and in a consanguineous Cambodian family with developmental glaucoma and severe corneal opacification. These results highlight the diverse ocular phenotypes caused by PXDN mutations, which are likely due to differences in genetic background and environmental factors. Peroxidasin is an extracellular matrix-associated protein with peroxidase catalytic activity, and we confirmed localization of the protein to the cornea and lens epithelial layers. Our findings imply that peroxidasin is essential for normal development of the anterior chamber of the eye, where it may have a structural role in supporting cornea and lens architecture as well as an enzymatic role as an antioxidant enzyme in protecting the lens, trabecular meshwork, and cornea against oxidative damage.

Adjuvant 5-fluorouracil in the treatment of localised ocular surface squamous neoplasia.

AIM: To report the outcome of treatment of localised non-invasive ocular surface squamous neoplasia (OSSN) where topical 5-fluorouracil (5-FU 1%) is used as an adjuvant to surgical excision. METHODS: The study was a prospective non-comparative interventional case series. 55 cases of primary localised OSSN and 10 cases of recurrent localised OSSN were treated with excision, cryotherapy and adjuvant 5-FU 1%. In all cases, irrespective of the involvement of surgical margins, a single cycle of 5-FU 1% was administered, four times a day for 2 weeks continuously. The main outcome measures were (1) recurrence and (2) complications related to adjuvant topical chemotherapy. Individuals were reviewed for a minimum of 12 months. RESULTS: There was a single case of recurrence (1.5%). 57% of patients had short-term complications secondary to 5-FU 1%, most frequently lid toxicity (49%), followed by superficial keratitis, epiphora and corneal epithelial defects. Four patients were unable to complete the course of 5-FU 1% because of local toxicity. CONCLUSIONS: The management of localised non-invasive OSSN with adjuvant 5-FU 1% was associated with a low rate of local recurrence. Although 5-FU 1% frequently results in short-term complications, most commonly lid toxicity, a full course is usually tolerated. Serious complications appear uncommon in the treatment of localised disease.

The differential diagnosis of localised amelanotic limbal lesions: a review of 162 consecutive excisions.

AIMS: To report the distribution of histopathological diagnoses in patients who underwent excision of localised limbal lesions that were clinically suspected to be squamous neoplasia (intra-epithelial neoplasia or squamous cell carcinoma). METHODS: 162 consecutive patients of a single ocular oncologist underwent an excisional biopsy between 1998 and 2009 for suspected squamous neoplasia. Histopathological reports were retrospectively reviewed. RESULTS: The population comprised 122 males and 40 females. The mean age was 63.4±15.8 (range: 27-90). 138 (85.2%) lesions were identified as intraepithelial neoplasia (CIN), of which 34 (21.0%) were CIN I, 32 (19.8%) were CIN II and 72 (44.4%) were CIN III or squamous cell carcinoma in situ. In seven (4.3%) cases, the lesion was invasive squamous cell carcinoma. In two (1.2%) cases, the lesion was amelanotic malignant melanoma. In 16 (9.9%) cases, histopathology revealed a benign entity including lesions described as squamous papilloma, solar elastosis and epithelial hyperplasia, keratosis or reactive atypia. CONCLUSIONS: In this population, for an experienced ocular oncologist, the misdiagnosis of localised limbal squamous neoplasia occurred in 10.5% of cases, with 5.5% of cases being malignant. This study highlights the importance of acquiring a clinical diagnosis before administering a topical chemotherapeutic agent.

Retrospective study of an as required dosing regimen of intravitreal bevacizumab in neovascular age-related macular degeneration in an Australian population.

PURPOSE: To investigate the efficacy of intravitreal bevacizumab for the treatment of neovascular age-related macular degeneration (AMD) using an as required dosing regimen. METHODS: A retrospective study of 210 patients (231 eyes) with choroidal neovascularization resulting from neovasacular AMD. Patients were treated with 1.25 mg intravitreal bevacizumab at a vitreoretinal practice in Adelaide, South Australia. Patients were followed up at 2-4 weeks and then at 1-month intervals; repeat injections were offered in the event of recurrence. Recurrence was defined as either a decrease of best-corrected visual acuity or an increase in macular oedema, subretinal fluid or intraretinal fluid on optical coherence tomography, after complete or partial resolution in previous follow-up visits. Patient data were collected for 12 months of follow up or until the patient's treatment was changed to ranibizumab. RESULTS: Significant improvement in visual acuity and central retinal thickness was demonstrated at 1 month with an improvement of vision from logMAR equivalent 0.76 to 0.68 (P < 0.001) and a decrease of central retinal thickness from 306 µm to 244 µm (P < 0.001). This overall improvement was continued throughout the 12-month follow-up period; however, follow up was poor with 12-month data available for only a small number of patients (7.8%). Ocular and systemic side-effects were rare at 3.5% and 0.4%, respectively. CONCLUSION: Eyes with neovascular AMD treated with intravitreal bevacizumab for up to 12 months had significant functional and anatomical improvement. Further studies need to confirm the long-term safety and efficacy of this treatment.

Mitomycin-C as adjuvant therapy in the treatment of sebaceous gland carcinoma in high-risk locations.

PURPOSE: To report on the use of Mitomycin-C as adjuvant therapy to excision and cryotherapy in patients with sebaceous gland carcinoma (SGC) in high-risk locations. DESIGN: Retrospective, consecutive, case series. PARTICIPANTS: Three patients with SGC of the upper palpebral conjunctiva or caruncle, but without clinical pagetoid spread. METHODS: Following excision and double freeze-thaw cryotherapy, patients with histology demonstrating SGC of the ocular surface were treated with topical Mitomycin-C (0.04%). Follow-up was conducted over an average of 30 months (range: 24-37 months). MAIN OUTCOME MEASURES: Postoperative evidence of local recurrence, lymph node or distant organ metastasis. RESULTS: No patients had evidence of local recurrence or systemic disease. CONCLUSIONS: Wide surgical excision with cryotherapy is the basis of treatment of SGC without pagetoid spread. The use of Mitomycin-C as adjuvant therapy remains controversial, although there is some rationale for its use in high-risk situations.

Cataract surgical coverage and self-reported barriers to cataract surgery in a rural Myanmar population.

PURPOSE: The aim of this study is to determine the cataract surgical coverage and investigate the barriers to cataract surgery as reported by those with cataract-induced visual impairment in rural Myanmar. METHODS: A cross-sectional, population-based survey of inhabitants 40 years of age and over from villages in the Meiktila District (central Myanmar); 2481 eligible participants were identified and 2076 participated. Data recording included corrected visual acuity, dilated slit lamp examination and stereoscopic fundus examination. Lens opacity was graded using the Lens Opacities Classification System III. Participants with cataract-induced visual impairment (acuity < 6/18 in better eye) were also invited to respond to a verbal questionnaire about barriers to cataract surgery. RESULTS: Cataract surgical coverage for visual acuity cut-offs of <6/18, <6/60 and <3/60 was 9.74%, 20.11% and 22.3%, respectively, for people and 4.18%, 9.39% and 13.47%, respectively, for eyes. Cataract surgical coverage was higher for men than women, but gender was not associated with refusal of services. Of the 239 who responded to the extra questionnaire, 216 were blind or had low vision owing to cataract. Three quarters refused referral for surgery: cost and fear of surgery were the most frequently reported barriers. CONCLUSION: Cost plays a large role in the burden of cataract in this region. Implementation of educational programmes, reforms to local health service and subsidization of ophthalmic care may improve the uptake of cataract surgery.

Treatment of radiation maculopathy with intravitreal injection of bevacizumab (Avastin).

PURPOSE: To evaluate the safety and efficacy of intravitreal injection of bevacizumab as a treatment option for radiation maculopathy secondary to plaque radiotherapy. METHODS: Interventional case series of five patients who developed radiation maculopathy complicating plaque radiotherapy with ruthenium 106 for choroidal melanoma. One to two intravitreal injections of bevacizumab (0.5 mL) were given, with an interval of 4 weeks between each injection. The main outcome measures were visual acuity and results of clinical ophthalmic examination and optical coherence tomography. RESULTS: Preinjection visual acuity ranged from hand movements to 20/25. The average preinjection central macular thickness measured by optical coherence tomography was 351 microm. Three of five patients had no improvement in macular edema after treatment with a single injection of bevacizumab at the 2-week follow-up (average postinjection central macular thickness, 287 microm). Maculopathy in these three patients was long-standing (3-5 years). Improvement in visual acuity occurred in two patients (from 20/30 to 20/25 and from 20/25 to 20/20). Maculopathy in these two patients was diagnosed 1 week before treatment was offered. Resolution of macular edema occurred after a single injection in Patient 4 and after two injections in Patient 5. Patient 4 did not receive direct radiation to the fovea. All but one patient (Patient 5; dose, 8,000 cGy) received a radiation dose of 10,000 cGy to the tumor apex. CONCLUSIONS: In this series, treatment of radiation maculopathy with intravitreal injection of bevacizumab was useful in two patients as measured by improvement in visual acuity due to resolution of macular edema. These patients were younger and had macular edema for a shorter duration. One patient did not receive direct radiation to the fovea, and the other had a lower dose of radiation.

Orbital plexiform neurofibroma and high axial myopia.

PURPOSE: To report a group of children with neurofibromatosis type 1 and orbital plexiform neurofibroma who developed axial myopia in the associated eye. METHODS: The clinical records and imaging of 3 patients with neurofibromatosis type 1 and orbital plexiform neurofibromas were reviewed. RESULTS: Three patients were identified who were diagnosed with orbital plexiform neurofibromas at the ages of 10 months, 9 months, and 16 years old. In all cases the axial length of the eye associated with the neurofibroma increased with length compared with the unaffected eye over time. Accordingly, the affected eye became increasing myopic with age, while the unaffected eye remained emmetropic. CONCLUSIONS: Eyes affected with orbital plexiform neurofibroma, a hallmark of neurofibromatosis type 1, appear to be associated with increased axial length and myopia. This is of particular importance in children, to diagnose and treat unilateral high myopia early and prevent anisometropic amblyopia.

Ethmoidal pneumocele following drainage of an ethmoidal mucocele.

Ethmoidal pneumocele is a rare condition with little known about its etiology. We report a 5-year-old boy who had recurrent right orbital cellulitis, non-axial proptosis, and inferolateral globe displacement. Initial radiological investigations demonstrated an ethmoidal mucocele. There was complete resolution of inflammatory signs with endoscopic drainage of the mucocele; however, repeat CT revealed a residual pneumocele with continued proptosis and lateral displacement of the globe. This case illustrates the potential for chronic sinusitis and iatrogenic drainage of an ethmoidal mucocele to progress to a pneumocele.

Awareness of diabetic eye disease among general practitioners and diabetic patients in Yangon, Myanmar.

BACKGROUND: Diabetes is an increasing problem in Myanmar with more than three million people affected. There are no data on awareness of diabetic retinopathy among the general practitioners (GPs) or diabetic population of Myanmar. This study aims to evaluate the awareness of diabetes-related eye disease among GPs and diabetic patients in Yangon, Myanmar. DESIGN: A cross-sectional survey. METHODS: From the Myanmar Medical Association Registry of 978 practicing GPs in Yangon, 200 were randomly selected and a structured questionnaire was sent to each. Each GP was asked to give a separate questionnaire to the first five diabetic patients who attended their practice. RESULTS: One hundred GPs and 480 patients returned the questionnaires. Although 99% of GPs were aware that diabetes could result in loss of vision, 49% never examined the fundi of their diabetic patients. Of the diabetic patients, 86% were aware that diabetes could damage their eyesight. Although 92% realized they should visit an ophthalmologist regularly, only 57% had seen an ophthalmologist. Patients who never attended school were less likely to visit an ophthalmologist than those with tertiary education (odds ratio 0.24; 95% confidence interval 0.09, 0.66). Patients with diabetes for less than 2 years were less likely to visit an ophthalmologist than those with diabetes for more than 10 years (odds ratio 0.21; 95% confidence interval 0.9, 0.44). There was no association between age, gender or work status and the likelihood of having seen an ophthalmologist. CONCLUSION: Although both GPs and diabetic patients are aware of the need for regular fundal screening, just over half the patients had been screened. There exists a need for programmes in Myanmar to induce a behavioural change in diabetic patients with regards to screening examinations.

Prevalence of trachoma-related trichiasis and corneal opacity in rural Myanmar: the Meiktila Eye Study.

OBJECTIVE: To describe the prevalence of trachomatous trichiasis and corneal opacity (CO) within central Myanmar. DESIGN: Population-based cross-sectional ophthalmic survey. PARTICIPANTS: Random, stratified, cluster sampling of the inhabitants > or =40 years of age from villages in the Meiktila District was performed; 2481 eligible participants were identified and 2076 participated in the study. METHODS: Visual acuity was measured using an E Snellen chart at 6 meters. Lid, ocular surface, and anterior segment examinations were performed at the slit lamp. MAIN OUTCOME MEASURES: Trachoma was graded as trachomatous trichiasis (TT) or CO according to the World Health Organization grading system. RESULTS: The population prevalence of trachoma (TT and CO) was 2.6% (95% confidence interval [CI]. 1.67%-3.42%). For every 1-year increase in age, the odds of trachoma increased by 5.3% (95% CI, 4.9%-5.7%). There was no significant effect of gender on the prevalence of trachoma (P = 0.5). No formal schooling was a strong predictor of trachoma (odds ratio, [OR], 4.9; 95% CI, 3.9-6.1), and having <3 children in the house was protective (OR, 0.75; 95% CI, 0.61-0.93); however, neither occupation nor the number of people in a household had an effect on trachoma. CONCLUSIONS: The prevalence of blinding trachoma in central Myanmar remains relatively low. This is a tribute to the success of the Burma Trachoma Control Program and demonstrates the need for such a program to remain an integral part of public health care and community health services to further diminish the prevalence of this condition. This will be facilitated by a focus on trachoma risk factors and further research into the prevalence of inflammatory trachoma within the pediatric population.

Successful treatment of a large choroidal abscess in an immunocompetent child. Treatment of a choroidal abscess.

BACKGROUND: We report the case of a systemically well 4-year-old Aboriginal boy who developed a choroidal abscess after being poked in the left eye with a blunt object. CASE REPORT: This boy presented with redness and reduced vision in the left eye after a blunt object was poked into his eye by his sibling. He was noted to have a choroidal mass which finally manifested as a choroidal abscess. RESULTS: His initial visual acuity was 6/60, and dilated fundus examination demonstrated a localised solid-appearing choroidal elevation involving the posterior pole, including the macula. An ultrasound of the eye revealed a choroidal haematoma with an atypical appearance, whose height was 8 mm with a base of 12 mm x 10 mm. The lesion failed to resolve, and eventually resulted in orbital cellulitis that did not respond to intravenous and topical antibiotic treatment. He then went on to achieve complete visual recovery after successful management by transcleral incision, drainage and systemic antibiotic therapy. CONCLUSION: Choroidal abscess has been described in patients who are debilitated, immunocompromised or suffer with systemic disease such as cystic fibrosis or endocarditis. This case represents a unique report of staphylococcal choroidal abscess in a healthy child that completely resolved after transcleral drainage and systemic antibiotics.

Congenital hypertrophy of the retinal pigment epithelium (CHRPE) in familial colorectal cancer.

BACKGROUND AND AIM: Congenital hypertrophy of the retinal pigment epithelium (CHRPE) is a pigmented fundus lesion associated with familial adenomatous polyposis (FAP). CHRPE prevalence has been reported to be increased in subjects with familial or sporadic non-polyposis colorectal cancer (CRC), suggesting that some individuals with non-polyposis CRC have an attenuated form of FAP. Other studies have not confirmed these clinical observations and have failed to identify mutations in the gene responsible for FAP, but the reason for the discrepancy in relation to CHRPE prevalence has not been resolved. We determined the prevalence of CHRPE in subjects without CRC (negative control cohort), subjects with FAP (positive control cohort), and subjects with familial non-polyposis CRC (test cohort). METHOD: A cohort study consisting of 37 negative control subjects, 9 positive control subjects with documented APC gene mutations, and 36 test subjects with familial non-polyposis CRC but no identified pathogenic APC gene mutation. The diagnosis of hereditary non-polyposis colon cancer was excluded in the test cohort by testing for microsatellite instability in tumour tissue. RESULTS: None of the 37 people in the negative control group had CHRPE. Five of nine (56%) patients with FAP had multiple CHRPE lesions. None of the 36 subjects in the test cohort had CHRPE lesions. CONCLUSIONS: Ophthalmoscopy may contribute to risk assessment in families with FAP but not in familial non-polyposis CRC. Care must be exercised when interpreting pigmented fundus lesions because 8-13% of subjects in each of the cohorts had pigmented retinal lesions that were not CHRPE. Bilateral lesions and lesions with a depigmented halo were the hallmarks of CHRPE associated with FAP.