Adam K Rudkin

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.

Vascular risk factors for central retinal artery occlusion

PurposeTo determine the proportion of patients presenting with thromboembolic central retinal artery occlusion (CRAO) who had undiagnosed vascular risk factors amenable to modification.MethodsA retrospective audit of consecutive patients with non-arteritic/thromboembolic CRAO presenting between 1997 and 2008 in a single tertiary teaching hospital.ResultsThirty-three patients with non-arteritic CRAO were identified. Twenty-one patients (64%) had at least one new vascular risk factor found after the retinal occlusive event, with hyperlipidemia being the most common undiagnosed vascular risk factor at the time of the sentinel CRAO event (36%). Nine patients (27%) had newly diagnosed hypertension or previous diagnosis of hypertension but not optimally controlled. To better control their vascular risk factors 18 patients (54%) were given a new or altered medication. Nine patients had more than 50% of ipsilateral carotid stenosis ; six of these proceeded with carotid endarterectomy or stenting. One patient had significant new echocardiogram finding. Systemic ischaemic event post CRAO occurred in two patients with stroke and acute coronary syndrome.ConclusionsPatients presenting with CRAO often have a previously undiagnosed vascular risk factor that may be amenable to medical or surgical treatment. As this population is at a high risk of secondary ischaemic events, risk factor modification is prudent.

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.

Prevalence of exfoliation syndrome in central Sri Lanka: the Kandy Eye Study

Aims: To report the prevalence and correlates of exfoliation syndrome (XFS) in central, rural Sri Lanka. Methods: A population-based, cross-sectional ophthalmic survey of inhabitants 40 years of age and over from villages in the Kandy District was conducted. Selection was randomised using a cluster sampling process. 1721 eligible participants were identified, 1375 participated. A detailed ophthalmic history and examination including ocular biometry was made of each participant. Results: The prevalence of XFS was estimated to be 1.1% (95% CI 0.5 to 1.5%; 22 eyes). XFS was bilateral in eight subjects, unilateral in six subjects. Univariate analysis demonstrated a significant association between XFS and increasing age (p<0.001), increasing intraocular pressure (odds ratio 1.2; 95% CI 1.09 to 1.27; p<0.001), nuclear cataracts (odds ratio 1.92; 95% CI 1.47 to 2.51; p<0.001), visual impairment (odds ratio 9.72; 95% CI 3.01 to 31.44; p<0.001) and a history of hypertension (odds ratio 3.89; 95% CI 1.14 to 13.16; p = 0.030). Conclusion: XFS in this Sri Lankan population was associated with advanced age, raised intraocular pressure, nuclear cataracts, hypertension and visual impairment.

Ocular neovascularization following central retinal artery occlusion: prevalence and timing of onset

Purpose Debate exists in the literature on the prevalence and etiology of neovascularization following central retinal artery occlusion (CRAO). The reported prevalence varies from 2.5% to 31.6%. We conducted a retrospective study to determine the prevalence of ocular neovascularization following acute CRAO in our institution. Methods A retrospective audit of consecutive patients with nonarteritic/thromboembolic CRAO presenting between 1997 and 2009 in a single tertiary teaching hospital. Results Thirty-three patients were identified as having nonarteritic CRAO, and of this cohort 6 patients (18.2%) developed ocular neovascularization. Neovascular glaucoma was present in 5 cases (15.2%); 2 of these presented through an emergency department with painful eyes, both at 16 weeks post CRAO. The other cases of neovascularization were detected on scheduled follow-ups. Mean time from retinal occlusive event to observed neovascularization was 8.5 weeks (range 2–16 weeks). One case of neovascularization was associated with hemodynamically significant ipsilateral carotid stenosis; no patient had proliferative diabetic retinopathy or other causes of neovascularization. Conclusions The prevalence of neovascularization following acute CRAO in our population was 18.2% at an average of 8.5 weeks post CRAO. There was a temporal relationship between the 2 events and no other causes of neovascularization demonstrable in our cohort of patients. There is no consensus on the follow-up regimen post CRAO to detect ocular neovascularization complications. Our study suggests that neovascularization can occur early and regular follow-up especially in the first 4 months is important post CRAO.

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

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.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.

Central retinal artery occlusion: timing and mode of presentation

Background and purpose:  Central retinal artery occlusion (CRAO) is a sudden, frequently irreversible, monocular vision loss, analogous to acute cerebral ischaemia. Thrombolysis may improve visual outcomes, but it is unclear what the acceptable timing of administration should be. We aim to ascertain, through audit, the timing and mode of presentation of individuals with potentially thrombolysable CRAOs.

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.

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.

Relapsing encephalopathy with headache: an unusual presentation of isolated intracranial neurosarcoidosis

We report a presentation of relapsing and remitting isolated intracranial neurosarcoidosis in a female patient who presented with episodic severe headache and behavioural disturbance initially misdiagnosed as psychosis. Eventually, several episodes were accompanied by visual disturbance secondary to papilloedema, ultimately leading to a diagnosis of neurosarcoidosis on meningeal biopsy. Sarcoidosis is a multisystem inflammatory disease of unknown aetiology, and is characterised by non-caseating granulomata. Pulmonary disease is the most common manifestation, occurring in 90% of patients. Clinical involvement of the nervous system is said to occur in 5–15% of patients.1 Isolated intracranial neurosarcoidosis is even rarer, with systemic sarcoidosis being detected in more than 95% of cases of sarcoidosis initially presenting with neurological symptoms.2 A woman presented initially at age 30 years, and then subsequently five times over 3 years with stereotyped episodes of headache, confusion and psychomotor agitation. In each instance, a history was given of a constant, severe bifrontal headache that was associated with nausea, vomiting, photophobia and/or visual field disturbance. As each presentation evolved, she became confused and encephalopathic. Early in the course of her illness these episodes were misinterpreted as acute psychosis because she exhibited pressured …