Orbital Exenteration for Advanced Periocular Adnexal Malignancies: Curative Versus Palliative Surgical Intent.

PURPOSE: To evaluate the survival benefit of orbital exenteration in periocular malignancy, taking account of preoperative intent. PATIENTS AND METHODS: Patients undergoing exenteration had retrospective chart review for demographics, clinical features, radiology, histology, and outcome. Based on systemic tumor status, the patient was either "Class I" (with absent or well-controlled systemic disease) or "Class II" (incurable active metastatic disease), and based on the extent of orbital disease and exenteration intent , was classed as either "Group A" (locally curative) or "Group B" (locally palliative). RESULTS: One hundred thirty-three patients (78 females; 59%) underwent exenteration at an average age of 61 years (median 64; range 5-91) for sebaceous, squamous and basal cell carcinomas, or for melanoma (22%, 19%, 11%, and 28%, respectively). There were 20% systemically incurable patients (26/133; Class II), and incurable local disease ("Group B") in 5% (5/107) of Class I and 15% (4/26) Class II patients. The overall survival (OS) was 88% at 12 months, 57% at 5 years, and 41% at 10 years, prognosis being worse with age more than 70 years ( p = 0.005), prior local radiotherapy ( p = 0.005) or positive resection margins ( p = 0.002). The mean OS for Type IA exenteration (145 months; 95% CI 122-168) was significantly different to 50 months for Type IB (95% CI 22-79; p = 0.02); likewise, OS for Type IIA procedures (31 months; 95% CI 11-51) was different to Type IIB (19 months; 95% CI 2-36) ( p = 0.001). CONCLUSION: Exenteration confers a significant survival with advanced periocular malignancies, even in patients with uncontrollable systemic disease, or where the local disease is deemed incurable.

Recurrent ptosis due to myopathy of the levator palpebrae superioris.

The authors report the 10-year follow-up of a case with a recurrent ptosis affecting both eyelids independently. The histology of the levator palpebrae superioris and Müller's muscle was consistent with a localised myopathic process. A therapeutic response to acetazolamide suggests that ion-channel dysfunction may be the underlying cause for this new myopathy.

Mucous membrane grafting.

INTRODUCTION: We review the use of mucous membrane grafting in the clinical management of dry eye-associated ocular surface disease. MATERIAL AND METHODS: Literature review of the scientific evidence, presentation of guidelines and surgical details. RESULTS AND CONCLUSION: The reformation and maintenance of a conjunctival fornix requires the addition of epithelial tissue, or a basement membrane which can be populated by healthy host epithelial cells. A healthy conjunctival or tarsal autograft, when available, is the ideal material. Oral mucosa does not contain goblet cells and therefore does not supplement the tear film: a full-thickness oral mucous membrane graft is the simplest graft to use if conjunctiva or tarsus is not available. Split-thickness mucosal grafts contract more, but are less bulky and pink than full-thickness grafts, and therefore should be used on the globe. Hard palate grafts are the thickest oral mucosal grafts and contract the least. Nasal mucosal grafts contain goblet cells that may contribute mucous to the tear film. This is maximised in turbinate mucosal grafts, which can relieve discomfort in extreme dry eye situations. Nasal septal cartilage contains fewer goblet cells, but adds rigidity. Amniotic membrane is thin and translucent-like conjunctiva, and possesses antiangiogenic, antiscarring and anti-inflammatory properties. It may become re-epithelialised with normal a conjunctival cell population and prevent postoperative cicatrisation, but requires the presence of healthy conjunctival stem cells to repopulate the graft, adequate lacrimal function to keep the graft moist, and a host site that is free from inflammation, otherwise it rapidly contracts. It can be combined with limbal transplantation and with an adjunctive antimetabolite.

Upper lid ptosis surgery: what is the optimal interval for the postoperative review? A retrospective review of 300 cases.

PurposeCorrection of upper eyelid ptosis is one of the most commonly performed oculoplastic procedures on the NHS but there is currently no data in the literature informing the surgeon of the optimal time for the first postoperative review. Our aim was to investigate how often a complication that warranted intervention occurred in the first 6 weeks after surgery and whether such a complication could have been predicted preoperatively.Patients and methodsA retrospective review was performed of 300 operations in 239 patients over a 9-month period at Moorfields Eye Hospital, London. Electronic medical record software was used to extract data regarding the timing of first postoperative review, complications, any return to theatre, and any underlying risk factors or co-morbidities.ResultsAt 1 week 44 % (133) cases were reviewed, 30% (89) at 2 weeks, 17% (50) at 3 weeks, and 9% (28) at 4 or more weeks. The overall complication rate at any time during the 6-week follow-up interval was 8%. The majority of these complications were minor (24 eyes, 8%) and 1 was major (0.3%). Of the 25 complications, an underlying risk factor was identified in 14 cases.ConclusionsThese data indicate that postoperative complications are very low in the absence of preoperative risk factors. In our institution, as the risk of overcorrection is low, most patients without risk factors for exposure (51% in this series) can safely be reviewed later than 1 week after surgery, but for those with risk factors earlier follow-up is warranted.

SOX2 anophthalmia syndrome: 12 new cases demonstrating broader phenotype and high frequency of large gene deletions.

BACKGROUND: Developmental eye anomalies, which include anophthalmia (absent eye) or microphthalmia (small eye) are an important cause of severe visual impairment in infants and young children. Heterozygous mutations in SOX2, a SOX1B-HMG box transcription factor, have been found in up to 10% of individuals with severe microphthalmia or anophthalmia and such mutations could also be associated with a range of non-ocular abnormalities. METHODS: We performed mutation analysis on a new cohort of 120 patients with congenital eye abnormalities, mainly anophthalmia, microphthalmia and coloboma. Multiplex ligation-dependent probe amplification (MLPA) and fluorescence in situ hybridisation (FISH) were used to detect whole gene deletion. RESULTS: We identified four novel intragenic SOX2 mutations (one single base deletion, one single base duplication and two point mutations generating premature translational termination codons) and two further cases with the previously reported c.70del20 mutation. Of 52 patients with severe microphthalmia or anophthalmia analysed by MLPA, 5 were found to be deleted for the whole SOX2 gene and 1 had a partial deletion. In two of these, FISH studies identified sub-microscopic deletions involving a minimum of 328 Kb and 550 Kb. The SOX2 phenotypes include a patient with anophthalmia, oesophageal abnormalities and horseshoe kidney, and a patient with a retinal dystrophy implicating SOX2 in retinal development. CONCLUSION: Our results provide further evidence that SOX2 haploinsufficiency is a common cause of severe developmental ocular malformations and that background genetic variation determines the varying phenotypes. Given the high incidence of whole gene deletion we recommend that all patients with severe microphthalmia or anophthalmia, including unilateral cases be screened by MLPA and FISH for SOX2 deletions.

Gorlin syndrome: the PTCH gene links ocular developmental defects and tumour formation.

AIM: To identify a gene linking microphthalmia with cyst with early onset medulloblastoma. METHODS: Mutation analysis of the PTCH gene. RESULTS: A mutation in exon 10 of the PTCH gene was identified, confirming a diagnosis of Gorlin syndrome. CONCLUSIONS: This is the first genetically identified mutation giving rise to microphthalmia with cyst and provides a valuable link in the eye developmental gene pathway.

Analysis of the phenotypic abnormalities in lymphoedema-distichiasis syndrome in 74 patients with FOXC2 mutations or linkage to 16q24.

INTRODUCTION: Lymphoedema-distichiasis syndrome (LD) (OMIM 153400) is a rare, primary lymphoedema of pubertal onset, associated with distichiasis. Causative mutations have now been described in FOXC2, a forkhead transcription factor gene. Numerous clinical associations have been reported with this condition, including congenital heart disease, ptosis, varicose veins, cleft palate, and spinal extradural cysts. SUBJECTS: We report clinical findings in 74 affected subjects from 18 families and six isolated cases. All of them were shown to have mutations in FOXC2 with the exception of one family who had two affected subjects with lymphoedema and distichiasis and linkage consistent with the 16q24 locus. RESULTS: The presence of lymphoedema was highly penetrant. Males had an earlier onset of lymphoedema and a significantly increased risk of complications. Lymphatic imaging confirmed the earlier suggestion that LD is associated with a normal or increased number of lymphatic vessels rather than the hypoplasia or aplasia seen in other forms of primary lymphoedema. Distichiasis was 94.2% penetrant, but not always symptomatic. Associated findings included ptosis (31%), congenital heart disease (6.8%), and cleft palate (4%). Other than distichiasis, the most commonly occurring anomaly was varicose veins of early onset (49%). This has not been previously reported and suggests a possible developmental role for FOXC2 in both venous and lymphatic systems. This is the first gene that has been implicated in the aetiology of varicose veins. CONCLUSION: Unlike previous publications, the thorough clinical characterisation of our patients permits more accurate prediction of various phenotypic abnormalities likely to manifest in subjects with FOXC2 mutations.

The incidence, embryology, and oculofacial abnormalities associated with eyelid colobomas.

PURPOSE: To describe a cohort of patients with congenital eyelid coloboma, to identify associated ocular and craniofacial abnormalities, and to establish any correlation between the size and location of eyelid colobomas and the presence of such abnormalities. METHODS: An observational case series of 55 patients with eyelid coloboma treated by a single surgeon (JROC) between 1985 and 2005. RESULTS: Eyelid colobomas predominantly affected the upper lids (93%), and were typically unilateral (76%). About a third (29%) were an isolated finding, with the remainder associated with other ocular (62%) and/or craniofacial (53%) abnormalities. Of those with ocular abnormalities; 19 (56%) had conjunctival traction bands, 16 (47%) choristomas, and 8 (24%) an abnormal globe. Of those with craniofacial abnormalities; 13 (45%) had Goldenhar Syndrome, 10 (35%) clefting disorders, and 4 (14%) Fraser Syndrome. Clefting disorders were typically associated with more severe colobomas and a higher incidence of conjunctival traction bands, first arch syndromes with smaller colobomas and more choristomas. Overall large colobomas were significantly associated with the presence of other craniofacial defects compared with small colobomas (P<0.01, χ(2)), but coloboma size did not correspond with the presence of other ocular abnormalities. CONCLUSIONS: Coloboma size, location, and associations in this series are consistent with our current understanding of eyelid embryogenesis. It is likely that those colobomas associated with other craniofacial and ocular abnormalities are those which result from errors earlier in embryogenesis during eyelid specification, growth, and closure, whereas isolated colobomas arise later during eyelid separation, and after codependent structures have developed.

Periocular tuberculous disease: experience from a UK eye hospital.

BACKGROUND/AIMS: To describe our experience of patients presenting to a tertiary referral adnexal department with orbital or periocular tuberculosis (TB) over a 10-year period. METHODS: We reviewed all patients with a diagnosis of orbital or periocular TB from 2001 to 2011 in Moorfields Eye Hospital. RESULTS: Nine patients were identified over the 10-year period. Three cases of cutaneous TB, two cases of TB dacryocystitis and four cases of diffuse orbital TB were identified. All patients lived in the UK, but were born in the African or Asian subcontinents. Three patients had known prior (and treated) pulmonary TB and all were immunocompetent.All patients presented with periocular discomfort. After tissue diagnosis, all patients were referred for triple antituberculous therapy (ATT); all patients completed their course of ATT, with resolution of all orbital and lacrimal masses. There were no recurrences at a median follow-up of 26 weeks (range 1 month-5 years). One patient, who required later evisceration, was the only case with loss of vision. CONCLUSIONS: Orbital and periocular TB can be difficult to diagnose and lead to diagnostic delays, with emphasis on clinical suspicion rather than a positive culture result; the management of such cases is not only surgical, but also medical and social. Although surgical intervention can alleviate symptoms and prevent visual loss, the use of a complete course of ATT is paramount for disease management and the patient and their family need to be counselled about the associated public health issues.

The management of orbital cysts associated with congenital microphthalmos and anophthalmos.

AIMS: To study the management of the orbital cysts present in a group of patients with anophthalmos and microphthalmos. METHODS: A retrospective study of 34 patients (40 orbits) treated for orbital cyst associated with microphthalmos and anophthalmos. RESULTS: The two largest treatment groups comprised 17 orbits (42.5%) where the cyst was removed surgically and 17 orbits (42.5%) where the cyst was retained and conformers were used. The remaining cases comprised two orbits (5%) where the cyst was aspirated initially; two orbits (5%) with large cysts which will need to be excised after further orbital growth; one orbit (2.5%) in which a silicone expander was used initially, and one orbit (2.5%) in which a mildly microphthalmic eye had some vision and was monitored but required no surgery. CONCLUSION: In this study 33 out of 34 patients had a good cosmetic result which illustrates that the orbital cyst in microphthalmos or anophthalmos performs a useful role in socket expansion and that the majority of patients with this condition can expect a good cosmetic outcome.

Costs and gains of complex procedures to rehabilitate end stage ocular surface disease.

BACKGROUND: The management of patients with end stage ocular surface disease sometimes requires extensive surgical treatment that can only be provided by specialised ophthalmology. The authors discuss the costs and gains of such complex techniques based on a case of bilateral corneal blindness secondary to Stevens-Johnson syndrome. METHODS AND RESULTS: Despite multiple lid surgery for trichiasis and repeated corneal grafting for perforations a white female patient became bilaterally blind at the age of 29 years. She also suffered from disabling discomfort in the right dry eye. At the age of 52 a two stage osteo-odonto-keratoprosthesis achieved visual rehabilitation in the left eye and microvascular transplantation of an autologous, submandibular gland resulted in sufficient lubrication to alleviate her severe discomfort in the right eye. As a result of these procedures she was able to take up a regular job again. The total costs of rehabilitation were pound 13 661 which compare with annual gains and regains for society of pound 13 497. An additional pound 4625 was saved annually in guide dog costs. CONCLUSION: This estimate shows that despite the expense of these complex techniques gains are made well within the second year after rehabilitation. In view of the benefit in quality of life for the patient and monetary savings for society these procedures should be funded by national health services at specialist centres.

Aetiology and surgical treatment of childhood blepharoptosis.

AIMS: To describe the aetiology, demography, surgical management, and outcome of a cohort of paediatric ptosis patients in a large tertiary referral oculoplastic centre. METHODS: A case note review of all patients undergoing ptosis surgery below the age of 16 years in a tertiary referral oculoplastic unit documenting the laterality, aetiology, severity of ptosis, indications for and type of surgery undertaken, the proportion of good, suboptimal, and poor surgical outcomes, re-operations, and level of patient satisfaction. RESULTS: 340 patients (82% (280/340) unilateral, 18% (60/340) bilateral ptosis) with myogenic (79%, 269/340), aponeurotic (5%, 16/340), neurogenic (11%, 37/340), mechanical (2%, 6/340), apparent (1%, 2/340), and syndrome related (3%, 10/340) ptosis underwent anterior (41%, 141/340) and posterior (26%, 90/340) levator resection, frontalis suspension with mersilene (9%, 29/340) and autogenous fascia lata (17%, 59/340), levator transposition (5%, 15/340) and other surgery (1%, 6/340) for visual (43%, 141/333) and cosmetic (57%, 189/333) indications. 77% (260/340) of patients achieved a good outcome, 10% (35/340) a suboptimal outcome, and 13% (45/340) a poor outcome requiring re-operation. There was no statistically significant difference in surgical outcome between patients with mild, moderate, or severe ptosis and with good, moderate, or poor levator function. The level of recorded patient satisfaction with the surgical outcome was 90% (206/229). CONCLUSIONS: Results suggest that most groups of paediatric ptosis patients, including those with poor levator function and severe ptosis, achieve satisfactory results with the appropriate ptosis surgery.

[Long-term follow-up after autologous submandibular gland transplantation in scarring keratoconjunctivitis with absolute dry eyes]. / Mehrjahresverlauf nach Autotransplantation der Unterkieferspeicheldrüse bei vernarbender Keratokonjunktivitis mit absolutem Tränenmangel.

INTRODUCTION: An autologous submandibular gland can be transplanted to the temporal fossa and following microvascular anastomosis to the temporal artery and vein and implantation of the secretory duct into the superotemporal conjunctival fornix to provide continuous substitute lubrication. Here we report our experiences with this procedure. PATIENTS AND METHODS: In a prospective, controlled clinical cohort study, we investigated the development of the Schirmer- test, fluorescein-break up time (F-BUT), degree of discomfort, use of pharmaceutical tear substitutes, visual acuity, Rose Bengal staining and conjunctival hyperemia in 14 eyes with a successful submandibular gland transplant and 11 dry eyes without salivary lubrication. RESULTS: Over a mean postoperative period of 3.3 years the transplantation group showed significant improvements of the Schirmer-Test, FBUT, use of pharmaceutical tear substitutes, discomfort and Rose Bengal staining up to the last follow-up when compared to the preoperative and control groups. CONCLUSION: Transplantation of an autologous submandibular gland can improve the lubrication and discomfort of absolute tear deficiency on a long term basis, but the salivary tear film only partially stabilises the ocular surface. The procedure is however able to provide symptomatic relief in extreme cases of absolute dry eyes.

Merkel cell tumour: case reports and review.

Merkel cell carcinoma, a small-cell undifferentiated/neuroendocrine carcinoma, is a highly invasive primary malignant neoplasm of the skin that may arise from Merkel cells or an epithelial precursor cell. One tenth of all cases affect the eyelids and periocular region, typically in the elderly population. The presentation is generally as a painless erythematous nodule with telangiectatic blood vessels and often intact overlying skin. The rarity of Merkel cell carcinoma of the eyelid can lead to delay in diagnosis and treatment of this tumour. In the present paper, the authors illustrate the aggressive nature of Merkel cell carcinoma, and the importance of early and wide surgical treatment and close follow-up. They discuss the role of rapid paraffin histology compared to frozen section. METHODS: Three cases are described, discussing the clinical presentation, diagnosis and treatment, with a review of the pathology. RESULTS: All three patients were female, presenting with rapidly growing upper eyelid tumours 20 mm in size; one case had paraffin sections suggesting incomplete clearance when frozen section had appeared clear; exenteration was required. The other two cases had lymph node involvement at one and two months post wide local excision. All patients remain alive at follow-up of 6, 4.6, and 2 years, respectively. DISCUSSION: The cases illustrate the aggressive nature of the tumour, the unusual tarsal involvement and the typical pathology. Sampling errors associated with limited frozen section control of excision may be avoidable by the use of rapid paraffin histology. The highly invasive nature of this tumour requires close follow-up following resection.

A practical guide to the management of anophthalmia and microphthalmia.

Congenital anophthalmia and microphthalmia are rare developmental defects of the globe. They often arise in conjunction with other ocular defects such as coloboma and orbital cyst. They may also be part of more generalised syndromes, such as CHARGE syndrome. Anophthalmia, microphthalmia, and coloboma are likely to be caused by disturbances of the morphogenetic pathway that controls eye development, either as a result of primary genetic defect, or external gestational factors, including infection or drugs that can influence the smooth processes of morphogenesis. The ophthalmologist is often the primary carer for children with anophthalmia and microphthalmia, and as such can coordinate the multidisciplinary input needed to offer optimal care for these individuals, including vision and family support services. They are able to assess the vision and maximise the visual potential of the child and they can also ensure that the cosmetic and social impact of anophthalmia or microphthalmia is minimised by starting socket expansion or referring to a specialist oculoplastics and prosthetics unit. A coordinated approach with paediatrics is necessary to manage any associated conditions. Genetic diagnosis and investigations can greatly assist in providing a diagnosis and informed genetic counselling.

Blepharospasm and hemifacial spasm: a protocol for titration of botulinum toxin dose to the individual patient and for the management of refractory cases.

PURPOSE: To evaluate a protocol for the treatment of facial dystonias. METHOD: A retrospective noncomparative interventional case series of all patients who attended a specialised tertiary referral clinic between January 2000 and January 2003. At the start of treatment, patients were seen and treated at weekly intervals until their symptoms were controlled or they developed complications. The sum of the weekly doses was taken as the individual patient dose and then given at 3-4 monthly intervals as required for the individual patient. Refractory cases of spasm underwent orbicularis muscle reduction. Pretarsal spasm was treated with pretarsal botulinum toxin. If the spasm was relieved but the patient could not open their eyelids, a trial of ptosis props was undertaken and the toxin injections continued, before considering a brow suspension. If patients could not see because of a spastic Bell's phenomenon, they were given centrally acting systemic medication. RESULTS: Of 182 new patients, 63 (35%) required two or more sets of injections to titrate their optimum dose of toxin. Symptoms improved in 169 patients (93%). Of a total 332 new patients and follow-up patients, 47 (14%) underwent surgery during their management, 36 protractor myectomy, and 13 brow suspension. Protractor myectomy improved symptoms in 23 (64%). Brow suspension improved symptoms in 12 patients (92%). CONCLUSIONS: The dose of botulinum toxin can be titrated to the individual patient, and the refractory cases managed satisfactorily if a logical protocol is followed.

An unusual ectodermal dysplasia with unique eye defects.

We report a 12-year-old boy with dental, auricular, nasolacrimal duct and unique eyelid anomalies as well as cribriform scrotal atrophy. We believe this is the first description of such a case, although many of the features fit within the spectrum of the ankyloblepharon/ectodermal dysplasia/clefting (AEC) syndrome.

Ophthalmic management of facial nerve palsy.

The ophthalmologist plays a pivotal role in the evaluation and rehabilitation of patients with facial nerve palsy. It is crucial to recognize and treat the potentially life-threatening underlying causes. The immediate ophthalmic priority is to ensure adequate corneal protection. The medium to long-term management consists of treatment of epiphora, hyperkinetic disorders secondary to aberrant regeneration and poor cosmesis. Patients should be appropriately referred for general facial re-animation. This review aims to provide a guide to the management of this complex condition.

Psychosocial distress associated with disfiguring eye conditions.

PURPOSE OF STUDY: Visible disfigurement is associated with a range of psychosocial difficulties; however, the problems encountered by patients with eye conditions are under-researched. This study aimed to establish the extent and type of psychosocial distress in this patient population, and to explore the extent to which patients' needs are currently met. METHOD: Standardised measures (anxiety, depression, appearance-related distress, and quality of life) and a semistructured interview (exploring individual experiences and satisfaction with care) were administered to 153 consecutive attenders at outpatient eye clinics in three different hospitals. Responses were analysed using descriptive statistics, multiple regression, and cluster analyses. RESULTS: Between 10 and 49% of the patient sample scored unfavourably on standardised measures in comparison with normative values. Cluster analyses revealed that more distressed patients typically exhibited higher levels of anxiety, depression, social anxiety, self-consciousness, and social avoidance. Quality of life scores were also less favourable. Distressed patients felt less well informed, less involved in their treatment, and less well supported in the clinic setting. Variability within the sample was high; however, the effects of the cause and duration of the condition were not significantly related to distress. Clinic staff identified a variety of constraints to meeting patients' need, including patient numbers, the lack of appropriate training, and the lack of referral possibilities. CONCLUSIONS: A considerable proportion of patients with disfiguring eye conditions experience high levels of psychosocial distress. Several options exist for ways in which patients' needs might more effectively be met within the constraints currently facing care providers.