Surgical intervention for paediatric blepharoptosis: a 6-year case series.

PURPOSE: To present our experience of paediatric blepharoptosis in a tertiary referral centre and evaluate the effectiveness of surgical intervention. METHODS: A retrospective cohort study of all children receiving surgical blepharoptosis correction between 1/1/10 and 29/2/16. Children with pre-operative levator function (LF) ≥ 7 mm received levator resection, those with LF ≤ 4 mm received brow suspension, and in those children with LF of 5-6 mm, either levator resection or brow suspension was chosen depending on the degree of frontalis recruitment. RESULTS: Ninety-five children (109 eyes, 64 boys) underwent blepharoptosis surgery within the study period. Mean (range) age at surgery was 5.9 (1.2-12.5) years. Seventy-nine (83.2%) had simple levator maldevelopment. Fifteen children were excluded due to inadequate follow-up. Of the remaining 80 children, 41 (51.2%) underwent levator resection, 27 (33.8%) underwent fascia lata brow suspension, and twelve (15.0%) underwent mersilene mesh brow suspension. Margin reflex distance-1 was greatest at 6-week follow-up with a small "lid drop" by 6-month follow-up in both the levator resection (0.9 mm pre-operatively, 3.1 mm at 6-week follow-up, 2.6 mm at 6-month follow-up) and fascia lata brow suspension (0.3 mm, 2.5 mm, 2.2 mm) groups. No immediate complications, and only two serious post-operative complications, were noted. One case of residual blepharoptosis was re-operated (fascia lata brow suspension). CONCLUSIONS: Surgical correction of paediatric blepharoptosis is safe and, after an observed lid drop between 6-week and 6-month follow-up (not seen in the mersilene mesh brow suspension group), effect appears to be maintained to 6 months and beyond. Readily accessible orthoptic assessment would help identify children at risk of amblyopia, both pre-operatively and post-operatively.

The intraoperative use of polydioxanone foil to reduce the risk of sino-orbital fistula formation in orbital exenteration.

BACKGROUND: Orbital exenteration is a radical surgical procedure resulting in deformity. It involves removal of the globe, optic nerve, extra-ocular muscles, orbital fat, lacrimal gland, and peri-osteum. Sino-orbital fistula (SOF) formation is a common documented post-operative complication, usually connecting the orbit and the ethmoid sinus. SOFs can cause leaks of serous fluid, and act as an entry site for pathogens into the orbit leading to socket infection and breakdown. METHODS: This retrospective study analyzed exenterations performed over a 22-year period (1993-2015) at the National Ocular Oncology Service Centre for Scotland. PDS is a crystalline, biodegradable polyether-ester that is strong with good shape-memory and flexibility. Orbital exenterations with and without the use of PDS foil were compared in terms of SOF formation. RESULTS: A total of 30 exenterations were performed during the study period. A total of 29 were analyzed. Choroidal malignant melanoma was the most common indication for performing orbital exenteration (n = 7, 24.14%). The most common post-operative complications seen were SOF (n = 8, 27.59%). A total of 8 out 21 (38.10%) cases not using PDS developed SOFs. By contrast, none of nine patients receiving PDS plates developed SOFs (p = 0.0332). CONCLUSIONS: This is the first study to compare SOF rate in patients undergoing exenteration with and without the use of PDS foil. PDS foil is a safe material, which has effectively reduced the incidence of SOF formation.

Pleomorphic adenomas of the lower eyelid: a case series.

Pleomorphic adenomas are well-recognized tumors usually arising within the main lacrimal gland. Their occurrence, however, is not limited to the main lacrimal gland. There have been cases reported in the eyebrow, upper eyelid, lateral lower eyelid, lacrimal sac, and even intraocularly. The medial aspect of the lower eyelid is a very rare site of occurrence because it is largely devoid of accessory lacrimal glands. We describe 2 cases of pleomorphic adenomas arising in the medial aspect and 1 case arising in the middle of the lower eyelid, respectively. The likely origin of these tumors at this location is from ectopic lacrimal gland.

Visual outcomes following orbital biopsy.

BACKGROUND: The risks of orbital biopsy depend on the lesion's location and relationship with surrounding structures. Complications include reduced vision, although visual outcomes following orbital biopsy are not widely reported. AIMS: To determine visual outcomes following orbital biopsy in Gartnavel General Hospital's Oculoplastic and Oncology Service. METHODS: Case note review of 50 consecutive patients undergoing orbital incision or excision biopsy between January 2006 and December 2010. Data collected included preoperative clinical examination, radiological and histological features, preoperative and postoperative corrected distance visual acuity (CDVA) and surgical complications. The main outcome measure was change in CDVA. Mean follow-up duration was 1.32 years. RESULTS: Histological diagnoses following biopsy included idiopathic orbital inflammation (n = 13) and lymphoma (n = 9). Of the radiologically defined lesions, 86.7% were extraconal (13.3% intraconal). Extraconal lesions were anterior in 59.0% (41.0% posterior). Mean preoperative LogMAR CDVA was 0.10 which was maintained at day one post-biopsy, indicating the absence of immediate sight-threatening complications such as retrobulbar haemorrhage or optic nerve compression, and there was no significant reduction at one-year follow-up (p = 0.239). Further analysis of change in CDVA showed no difference between: anterior and posterior lesions; extraconal and intraconal lesions; incision and excision biopsies; anterior and lateral surgical approaches. CONCLUSIONS: CDVA is retained for one year following orbital biopsy. Significant visual loss is a very rare complication of this procedure.

Corneal perforation due to limbal involvement in Sézary syndrome.

BACKGROUND: The majority of lymphomas involving the eye and ocular adnexa are B-cell lymphomas. Ocular involvement by T-cell lymphoma is rare. We report a case of corneal perforation due to direct involvement of the corneal limbus by lymphoma in a patient with Sézary syndrome. METHODS: A 58-year-old male with cutaneous T-cell lymphoma presented with painful, left-sided corneal ulceration, a dense infiltrate, severe epitheliopathy, hypopyon and a diffuse confluent dermatitis involving the lids. He had a history of Sézary syndrome. Despite maximal treatment, this severe ulcerative keratitis progressed to central corneal perforation. The eye was subsequently enucleated and submitted for histopathological examination. RESULTS: Histopathological examination confirmed corneal ulceration with perforation. There was an infiltrate of large atypical cells at the limbus, with tropism for the overlying epithelium. Immunohistochemical staining of these cells was positive for CD2, CD3, CD5, CD4 and CD7. Staining for CD8, CD30 and CD56 was negative. The appearances were those of an epitheliotrophic T-cell lymphoma, and were considered to represent spread from the patient's underlying Sézary syndrome. The patient died 2 months later from bronchopneumonia. CONCLUSIONS: Ocular involvement by cutaneous T-cell lymphoma usually occurs in advanced disease, and carries a poor prognosis. This patient was immunocompromised due to advanced malignancy, and there was a high suspicion of infection as the primary cause of corneal ulceration. This case highlights that it is important to consider direct tumour infiltration as an initiating or contributing factor for corneal ulceration in such patients.

A bilateral cicatricial ectropion and bilateral upper lid shortening caused by 5-fluorouracil toxicity in a patient with dihydropyrimidine dehydrogenase deficiency.

CONTEXT: Well-known causes of a cicatrizing ectropion are chemical/thermal injuries, dermatitis, cutaneous diseases, malignancies, and trauma. We add to this preceding list a systemic cause of a cicatrizing ectropion as a result of a rare side effect of 5-fluorouracil (5-FU), a common and frequently used chemotherapeutic agent. METHODS: A case report demonstrating the clinical presentation of a cicatricial ectropion caused by (5-FU) chemotherapy toxicity in a patient with dihydropyrimidine dehydrogenase deficiency. We also describe the subsequent investigations and management of this case. RESULTS: A bilateral cicatrizing lower lid ectropion, bilateral upper lid shortening, cicatrizing and sclerosing facial skin changes occurred in an 80-year-old male, undergoing preoperative chemoradiotherapy, incorporating Capecitabine, an oral 5-FU prodrug for a locally advanced rectal carcinoma. Severe 5-FU toxicity ultimately proved fatal but in addition to typical 5-FU related adverse effects, the patient developed bilateral incomplete lid closure, secondary corneal exposure and keratopathy. Due to the patient's extreme ill health, he was managed conservatively with a moist chamber. CONCLUSION: 5-fluorouracil chemotherapy in patients with dihydropyrimidine dehydrogenase deficiency, can give rise to ocular and cutaneous toxicity. We also present the complex management problems that have to be anticipated in treating such systemically compromised patients.

Low dose orbital radiotherapy for thyroid eye disease.

PURPOSE: The use of low dose orbital radiotherapy for thyroid eye disease (TED) remains controversial. This is a review of patients with TED treated with radiotherapy in our department over the last twelve years. METHODS AND MATERIALS: Fifty-nine consecutive patients received low dose orbital radiotherapy of 20 Gray (Gy) for active TED at the Beatson Oncology Centre. Their records were retrospectively reviewed and data including duration of symptoms, clinical activity score (CAS) pre- and post-orbital radiotherapy, immunosuppression requirement, subjective assessment and range of rehabilitative surgery was collected. RESULTS: Before orbital radiotherapy, all fifty-nine patients had an initial response to glucocorticoids and therefore presumed to have active phase thyroid eye disease. They received retro-orbital radiotherapy of 20 Gy in 12 fractions over 2 weeks. After treatment, only five patients remained on steroids and only one patient had CAS ≥ 3 at last follow up. Response (change in CAS) to orbital radiotherapy was statistically significant from 3.17 ± 1.75 standard deviation (SD) to 0.73 ± 0.92 SD (P < 0.001) at mean follow up of 6.5 months. There was a reduction in CAS at each subsequent follow up for all subgroups when the patients were grouped according to disease severity i.e. mild TED(CAS 1-2), moderate (CAS 3-4), severe CAS (5-7) and optic neuropathy. CONCLUSIONS: We believe orbital radiotherapy has a definite role to play in the treatment of active thyroid eye disease. The majority of our patients experienced a reduction in their clinical activity scores after orbital radiotherapy and this was irrespective of the severity of thyroid eye disease.

Recurrent choroidal melanoma after transscleral local resection with diffuse vitreous seeding.

BACKGROUND: Choroidal melanoma usually spreads systemically via the vascular system or extraocularly through channels in the sclera. Intraocular spread through vitreous seeding is uncommon. METHODS: We present two patients in whom melanoma recurred following transscleral local resection and widespread fine patchy pigmentation of the retina was identified grossly. The eyes were submitted for histological examination. RESULTS: In one case there was recurrent melanoma in the surgical coloboma with diffuse vitreous seeding and a pre-retinal membrane composed of tumour cells. Tumour cells were also identified in the anterior chamber. In the second case there was no tumour in the coloboma although two small satellite choroidal nodules were identified. Tumour cells were also present in the vitreous and covering the surface of the retina. CONCLUSIONS: We described two cases of recurrent choroidal melanoma following transscleral local resection with vitreous seeding. Intraocular seeding following local resection is uncommon. There are several potential mechanisms for this although it seems likely that in these cases loss of the retinal barrier assisted in the intraocular spread of these tumours.

Successful medical treatment of blepharochalasis: a case series.

INTRODUCTION: Blepharochalasis describes recurrent attacks of idiopathic transient painless oedema in the adnexal tissue of the orbit with the most severe reaction in the skin and orbicularis region. This may produce permanent tissue changes associated with thinning of the eyelid skin. Previous reviews have concentrated on surgical correction of the excess skin and orbicularis created by the condition. There has, as yet, been no report of successful medical management. PATIENTS AND METHODS: We report here on 4 males and 2 females aged between 37 and 78 years. Systemic acetazolamide (initially 250 mg SR OD), was used in combination with a topical steroid (hydrocortisone cream). RESULTS: All 6 patients achieved relief of their symptoms, with decreased incidence of occurrence and duration of episode if not complete resolution. CONCLUSION: Oral Acetazolamide in combination with topical hydrocortisone provides effective relief of the periorbital oedema associated with blepharochalasis. In our short series, the cases were improved either with medical therapy alone or in combination with surgery. Relapses following surgery were diminished as a result of prior medical therapy.

Uveal melanoma-associated survival in Scotland.

BACKGROUND/OBJECTIVES: The Scottish Ocular Oncology Service (SOOS) manages all patients with uveal melanoma (UM) in Scotland. Our aim was to determine the long-term all-cause and cause-specific survival of patients with UM, irrespective of treatment modality. SUBJECTS/METHODS: A retrospective single-centre cohort study including all patients diagnosed with UM by the SOOS between 1/1/1998 and 31/12/2002. Data from the SOOS database were correlated with death records held by National Records of Scotland, which provided date, and all listed causes, of death for all deceased patients. RESULTS: Two hundred and eighteen patients were newly diagnosed with UM between 1/1/1998 and 31/12/2002. One hundred and fifteen (52.8%) were female. The mean (median) age at diagnosis was 63(65) years (range: 16-89). Of 179 choroidal melanomas, melanoma-specific survival was 92.3%, 87.4% and 83.8% at 5, 10 and 15 years, respectively. Cancer-specific survival was 85.8%, 71.8% and 62.3%. All-cause survival was 81.6% (146/179), 62.0% (111/179) and 46.7% (computed, fraction inexpressible). Of 26 ciliary body melanomas, melanoma-specific survival was 87.2%, 81.3% and 81.3% at 5, 10 and 15 years. Cancer-specific survival was 62.9%, 40.6% and 40.6%. All-cause survival was 61.5% (16/26), 38.5% (10/26) and 26.9% (7/26). Of 13 iris melanomas, at all three timepoints (5/10/15 years), melanoma-specific survival was 100%, cancer-specific survival was 92.3%, and all-cause survival was 76.9% (10/13). CONCLUSIONS: Correlation of SOOS and national records survival data confirms 15-year melanoma-specific survival of 83.8%, 81.3% and 100% for choroidal, ciliary body and iris melanomas, respectively. We can now provide accurate survival data to our patients in Scotland.

Use of Ruthenium-106 Brachytherapy for Iris Melanoma: The Scottish Experience.

PURPOSE: To analyse long-term outcomes of ruthenium-106 (106Ru) plaque brachytherapy for the treatment of iris melanoma. METHODS: We retrospectively reviewed medical records of 19 consecutive patients with pure iris melanoma treated with 106Ru plaque brachytherapy between 1998 and 2016 at the Scottish Ophthalmic Oncology Service, Glasgow. The iris melanoma was treated with a ruthenium plaque placed on the corneal surface to deliver a surface dose of 555 Gy. We analysed vision preservation, local tumour control, radiation-related complications, eye retention rates, symptomatic metastasis and melanoma-related mortality. RESULTS: The mean largest basal diameter of the lesions was 3.50±1.42 mm (range 1.6-6.5 mm), and the mean maximum height was 1.47±0.65 mm (range 0.7-2.8 mm). The tumour control and eye retention were 100% at a mean follow-up of 62 months (range 6-195 months). A 62% reduction in tumour height was observed on ultrasonography. Complications included cataract (68%), dry eye (47%), uveitis (37%) and scleral thinning (5%). At the final follow-up visit, the mean loss of Snellen visual acuity was 1.11±2.90 lines and vision of 6/9 or better was maintained in 53% of patients. None of the patients had evidence of symptomatic metastasis (non-imaged) or melanoma-related mortality. CONCLUSIONS: 106Ru plaque treatment for iris melanoma was highly effective a high tumour control, no tumour recurrences and a relatively a low complication rate.

Combined immunosuppression and radiotherapy in thyroid eye disease (CIRTED): a multicentre, 2 × 2 factorial, double-blind, randomised controlled trial.

BACKGROUND: Standard treatment for thyroid eye disease is with systemic corticosteroids. We aimed to establish whether orbital radiotherapy or antiproliferative immunosuppression would confer any additional benefit. METHODS: CIRTED was a multicentre, double-blind, randomised controlled trial with a 2 × 2 factorial design done at six centres in the UK. Adults with active moderate-to-severe thyroid eye disease associated with proptosis or ocular motility restriction were recruited to the trial. Patients all received a 24 week course of oral prednisolone (80 mg per day, reduced to 20 mg per day by 6 weeks, 10 mg per day by 15 weeks, and 5 mg per day by 21 weeks) and were randomly assigned via remote computerised randomisation to receive either radiotherapy or sham radiotherapy and azathioprine or placebo in a 2 × 2 factorial design. Randomisation included minimisation to reduce baseline disparities in potential confounding variables between trial interventions. Patients and data analysts were masked to assignment, whereas trial coordinators (who monitored blood results), pharmacists, and radiographers were not. The radiotherapy dose was 20 Gy administered to the retrobulbar orbit in ten to 12 fractions over 2 to 3 weeks. Azathioprine treatment was provided for 48 weeks at 100-200 mg per day (dispensed as 50 mg tablets), depending on bodyweight (100 mg for <50 kg, 150 mg 50-79 kg, 200 mg for ≥80 kg). The primary outcomes were a binary composite clinical outcome score and an ophthalmopathy index at 48 weeks, and a clinical activity score at 12 weeks. The primary analysis was based on the intention-to-treat allocation and safety was assessed in all participants. This study is registered with ISRCTN, number 22471573. FINDINGS: Between Feb 15, 2006, and Oct 3, 2013, 126 patients were recruited and randomly assigned to groups: 31 patients to radiotherapy plus azathioprine, 31 to sham radiotherapy and azathioprine, 32 to radiotherapy and placebo, and 32 to sham radiotherapy and placebo. Outcome data were available for 103 patients (54 for sham radiotherapy vs 49 for radiotherapy and 53 for placebo vs 50 for azathioprine), of whom 84 completed their allocated treatment of radiotherapy or sham radiotherapy and 57 continued to take azathioprine or placebo up to 48 weeks. There was no interaction betweeen azathioprine and radiotherapy (pinteraction=0·86). The adjusted odds ratio (ORadj) for improvement in the binary clinical composite outcome measure was 2·56 (95% CI 0·98-6·66, p=0·054) for azathioprine and 0·89 (0·36-2·23, p=0·80) for radiotherapy. In a post-hoc analysis of patients who completed their allocated therapy the ORadj for improvement was 6·83 (1·66-28·1, p=0·008) for azathioprine and 1·32 (0·30-4·84, p=0·67) for radiotherapy. The ophthalmopathy index, clinical activity score, and numbers of adverse events (161 with azathioprine and 156 with radiotherapy) did not differ between treatment groups. In both groups, the most common adverse events were mild infections. No patients died during the study. INTERPRETATION: In patients receiving oral prednisolone for 24 weeks, radiotherapy did not have added benefit. We also did not find added benefit for addition of azathioprine in the primary analysis; however, our conclusions are limited by the high number of patients who withdrew from treatment. Results of post-hoc analysis of those who completed the assigned treatment suggest improved clinical outcome at 48 weeks with azathioprine treatment. FUNDING: National Eye Research Centre, Above and Beyond, and Moorfields Eye Charity.

The T1799A BRAF mutation is present in iris melanoma.

PURPOSE: An activating mutation in exon 15 of the BRAF gene has been found in a high proportion of cutaneous pigmented lesions, but only in one case of uveal melanoma. Iris melanoma is the least common uveal melanoma and displays a less aggressive clinical course compared with posterior uveal melanoma. To date, no study has been conducted to investigate the T1799A mutation in iris melanoma. The purpose of this study was to determine whether the T1799A BRAF mutation is present in iris melanoma. METHODS: DNA was extracted from 19 archival, paraffin-embedded tissue sections of iris melanomas. Nested PCR was used to amplify exon 15 of the BRAF gene, and the product was purified, cloned into a sequencing vector, and sequenced. The sequences obtained were compared with the wild-type sequence of the BRAF gene. The presence or absence of the BRAF mutation was also compared with the clinicopathological features. RESULTS: The T1799A mutation was identified by sequencing in 9 of 19 iris melanomas. Six of the 9 cases with the BRAF mutation were recurrent tumors. All other tumors were resections for primary tumors. There was a statistically significant association between the BRAF mutation and recurrent tumor (P = 0.003). There was no association between the presence of the BRAF mutation and other clinicopathological characteristics. CONCLUSIONS: In this small study, the T1799A BRAF mutation was identified in almost half of the iris melanoma tissues samples examined. This finding suggests that there may be genetic as well as clinical differences between iris and posterior uveal melanomas.

Repeatability and reproducibility of macular thickness measurements with the Humphrey OCT system.

PURPOSE: To assess the accuracy, precision, repeatability, and reproducibility of measurements made by the Humphrey optical coherence tomography (OCT) system (Humphrey-Zeiss Medical Systems, San Leandro, CA). METHODS: The performance of the system was first investigated by scanning a test object containing an air gap of known size. Measurements were repeated with water or glycerin in the gap. In the clinical setting, macular thickness measurements were obtained from a control group of 20 normal subjects. For analysis, these scans were divided into eight sections, each containing 10 A-scans. RESULTS: The average gap thickness was found to be close to the true value in all cases. The overall coefficients of intersession reproducibility were less than 1% for the test object and 1.51% for the control group. There was no significant difference between scans acquired during different sessions. The overall coefficients of repeatability for the test object were between 0.2% and 1.1% and between 1% and 2% for the control group. The range of normal retinal thickness in terms of the 5th and 95th percentiles was 222 to 248 microm in women and 234 to 257 microm in men. CONCLUSIONS: Measurements made from OCT scans were found to be accurate and precise. Introducing water or glycerin into the test object resulted in considerable degradation of the signal, but measurements of gap thickness were still shown to be accurate, precise, reproducible, and repeatable. Retinal thickness measurements in the macular area were repeatable and reproducible. This demonstrates that OCT is a useful tool in the monitoring of patients with conditions that affect macular thickness, even when there is considerable degradation of the OCT signal.

BRAF mutations in conjunctival melanoma.

PURPOSE: An activating mutation in exon 15 of the BRAF gene has been found in a high proportion of cutaneous melanomas and cutaneous nevi but not in uveal melanoma. Conjunctival melanoma shows greater clinical similarity to cutaneous melanoma than does uveal melanoma. The purpose of this study was to determine whether the T1799A BRAF mutation found in cutaneous melanoma is also present in conjunctival melanoma. METHODS: DNA was extracted from paraffin sections obtained from glutaraldehyde or formalin-fixed, paraffin-embedded conjunctival melanomas. Forty-two specimens were identified from 25 patients. Seminested PCR was used to amplify exon 15 of the BRAF gene, and the resultant PCR product was purified and directly sequenced. Sequences from conjunctival melanomas were compared with the wild-type sequence of the BRAF gene. The presence or absence of the BRAF mutation was compared with the clinicopathological features. RESULTS: The T1799A (V600E) mutation was detected by sequencing in melanomas from 5 of 22 patients as well as in the positive control, a cutaneous melanoma cell line. In this small series, no statistically significant associations between the presence of the BRAF mutation and clinicopathological characteristics were detected, although tumors with this mutation tended to have a larger diameter and greater depth of invasion and to contain epithelioid cells. CONCLUSIONS: Others have demonstrated a BRAF T1799A-activating mutation in cutaneous but not uveal melanoma. In this study, this BRAF mutation was demonstrated in some conjunctival melanoma tissue samples, suggesting that some conjunctival melanomas may share biological features in common with cutaneous melanoma.

Repeatability and reproducibility of corneal thickness measurements by optical coherence tomography.

PURPOSE: To assess the repeatability and interoperator and intersession reproducibility of central corneal thickness (CCT) measurements made by a commercially available optical coherence tomography (OCT) system. METHODS: Intersession and interoperator reproducibility and repeatability were defined according to the guidelines of the British Standards Institution and examined in a control group of 14 normal subjects. An in-house computer program was used to evaluate central corneal thickness from these scans. RESULTS: The coefficient of interoperator reproducibility was 0.18%, whereas that for intersession reproducibility was 1.11%. Wilcoxon analysis (5% level of significance) showed that there was no statistically significant difference between scans acquired during different sessions or by different operators. Coefficients of repeatability were all less than 3%. The average CCT was 526 +/- 28 microm (SD) and the range of normal CCT between 5th and 95th percentiles was 498 to 576 microm. CONCLUSIONS: Although the commercially available OCT scanner was designed for retinal imaging, with a few minor modifications, the system may be used to image the anterior segment. Previous studies have shown that OCT measurements correlate well with those from conventional techniques, and it has the added advantage of being a noncontact technique. This study further demonstrates that the OCT measurements show a high degree of repeatability and reproducibility. Thus, OCT is emerging as a promising tool for evaluation of CCT in the clinical setting.