Diagnosis of Alagille syndrome-25 years of experience at King's College Hospital.

OBJECTIVE: The aim of the study was to study the clinical and histological features of Alagille syndrome (AGS) at presentation comparing the value of the various modalities before the implementation of genetic diagnosis. PATIENTS AND METHODS: We performed a retrospective analysis of the records of 117 children diagnosed as having AGS after referral to King's College Hospital between 1980 and 2005. RESULTS: Cholestasis was seen in 104 of 117 (89%), characteristic facies in 91 of 117 (77%), posterior embryotoxon in 72 of 117 (61%), butterfly vertebrae in 44 of 117 (39%), heart disease (most often peripheral pulmonary stenosis) in 107 of 117 (91%), and renal disease in 27 of 117 (23%). Serum cholesterol levels of >5 mmol/L were seen in 52 of 86 (60.4%). Liver biopsy showed characteristic features of paucity of interlobular bile ducts in 59 of 77 (76.6%) children younger than 16 weeks of age, in 10 of 14 (71.4%) between 16 weeks and 1 year of age, and in 8 of 12 (66.66%) older than 1 year of age. Other biopsy findings were those of nonspecific hepatitis and biliary features. Iminodiacetic acid scans showed no excretion of isotope into the bowel after 24 hours in 21 of 35 (60%), and small/no gallbladder on ultrasound was seen in 29 of 104 (27.8%). Eleven of 117 (9.4%) had a diagnostic laparotomy and operative cholangiography, 2 proceeding to Kasai portoenterostomy before referral to our unit. CONCLUSIONS: Clinical features of AGS are not as consistently informative as suggested in the literature. Hypercholesterolaemia is nonspecific but may be a helpful pointer. Histology is not characteristic in 25%; hepatobiliary iminodiacetic acid scan and ultrasound may suggest a false diagnosis of biliary atresia in 60% and 28%, respectively, supporting the concept that infants with liver disease warrant early referral to a specialist centre. The advent of genetic diagnosis will redefine the syndrome with likely effects on the prognosis of the defined group.

Ocular abnormalities in Alagille syndrome.

OBJECTIVE: To assess the type and frequency of ocular abnormalities occurring in Alagille syndrome (AS) in a large group of affected patients and their parents and the potential pathogenetic role of fat-soluble vitamin deficiency. DESIGN: Observational case series. PARTICIPANTS: Twenty-two children with AS and 23 of their parents participated. MAIN OUTCOME MEASURES: Participants underwent full ophthalmic examination, including refraction, orthoptic examination, keratometry, slit-lamp examination, and funduscopy. Corneal diameter measurement was performed in a subset of nine and fluorescein angiography in a subset of six. Serum levels of vitamins A and E and cholesterol were measured. RESULTS: The most common ocular abnormalities in patients with AS were posterior embryotoxon (95%), iris abnormalities (45%), diffuse fundus hypopigmentation (57%, a previously unreported finding), speckling of the retinal pigment epithelium (33%), and optic disc anomalies (76%). Microcornea was not associated with large refractive errors, and visual acuity was not significantly affected by these ocular changes. Vitamin levels were normal. Ocular abnormalities including posterior embryotoxon, iris abnormalities, and optic disc or fundus pigmentary changes were detected in one parent in 36% of cases. CONCLUSIONS: Alagille syndrome is associated with a characteristic group of ocular findings without apparent serious functional significance and probably unrelated to fat-soluble vitamin deficiency. Simple ophthalmic examination of children with neonatal cholestatic jaundice and their parents should allow early diagnosis of AS, eliminating the need for extensive and invasive investigations.

Transscleral diode laser in the treatment of retinopathy of prematurity.

PURPOSE: To assess the outcome of contact transscleral diode laser (TSDL) in the treatment of threshold retinopathy of prematurity (ROP). METHOD: TSDL was performed in 14 eyes of 8 babies who presented to the paediatric ophthalmic service at King's College Hospital between 1996 and 1997 with threshold ROP (median post-conceptual age 26 + 1 weeks, median birthweight 835 g) by a single surgeon. Follow-up ranged from 9 to 41 weeks (median 21 weeks). RESULTS: In 11 eyes (79%) regression of ROP occurred after a single laser treatment with a good anatomical outcome. In 3 eyes (21%) there was an unfavourable response with the development of traction retinal detachment. These include both eyes of one baby who rapidly progressed to stage IV ROP. One other eye developed a fibrotic band a few months after treatment. No significant complications of laser treatment were observed. CONCLUSION: These initial results indicate that TSDL photocoagulation is an effective and technically straightforward alternative to cryotherapy in the treatment of ROP.

Sickle Cell Retionapathy

We have conducted screening programmes at King's College Hospital for the assessment of the ocular manifestations of sickle cell disease in adults as well as in children. We have followed the same protocol used in the cohort study carried out in Jamaica. Fundus flourescein angiograms were performed on patients over the age of five. Our findings were compared to those of the Jamaican cohort. The studies were agreed by the Medical ethical committee at King's College Hospital. Some of the results have already been published. We have also documented some cases of retionopathy in patiens with AS and AC haemoglobinopathy. The eye is an invaluable window that provides an opportunity to assess the presence and progression of small vessel disease. The ocular manifestations of sickle cell haemoglobinopathies provide useful clues to the understanding of this condition. I propose to present a summary of our results so far. This study was supported by the locally organized research scheme and was conducted in association with Professor Alastair Bellingham and Dr. Arya from the Haemotology department at King's College Hospital and Professor A C Bird from Moorfields eye Hospital.(AU)

Ocular ultrasound in Alagille syndrome: a new sign.

BACKGROUND: Alagille syndrome (AS) is one of six forms of familial intrahepatic cholestasis, all of which present with neonatal jaundice and paucity of intrahepatic bile ducts. Differentiation of these individual syndromes is crucial as their treatments and prognoses vary. It is the ophthalmic features, posterior embryotoxon on particular, that distinguish AS. METHODS: The authors performed full ocular examination, including A- and B-scan ultrasound, refraction, and, where possible, fluorescein angiography in 20 unrelated children with AS and 8 with non-AS-related cholestasis. RESULTS: There was ultrasound evidence of optic disc drusen in at least one eye in 95% and bilateral disc drusen in 80% of patients with AS but in none of the patients who were non-AS at the time of examination. Independent review of hard-copy scans suggested drusen in at least one eye in 90% of the cases and bilateral drusen in 50%, although this latter figure rose to 65% on review of the angiograms. This is markedly higher than the incidence in the normal population (0.3%-2%). Axial lengths were shorter than expected for the older age group (older than 10 years of age), but this was not associated with gross ametropia. CONCLUSION: This strong association of AS and optic disc drusen has not been reported previously and represents not only the first significant association between a systemic condition and disc drusen but also a possibly useful tool in the diagnosis of AS, especially in young children.

Topical steroid use in the treatment of ocular alkali burns.

BACKGROUND: Ocular alkali burns can be associated with a poor visual outcome. The release of collagenases and proteases after the injury leads to corneoscleral melting. The role of topical steroids in such patients is controversial as they have been postulated to exacerbate corneoscleral melting. METHODS: 30 patients were reviewed retrospectively after admission to King's College Hospital with alkali burns between 1990 and 1993. All patients were treated with an intense and prolonged regimen of topical steroids and topical and systemic vitamin C. RESULTS: 22 patients had mild injuries and eight had severe injuries as estimated by the Roper-Hall grading system. 23 patients were treated with topical steroids for > 10 days and 22 patients were treated with topical vitamin C for more than 10 days. One patient with a severe injury developed corneoscleral melting. CONCLUSION: Prolonged treatment with topical steroids when used in conjunction with topical vitamin C is not associated with corneoscleral melting.

Retinopathy in haemoglobin C trait.

Retinopathy associated with sickle-C and sickle cell disease is well described. Sickle trait and haemoglobin C trait are generally considered benign conditions, with infrequent systemic manifestations. Rare cases of retinopathy in sickle trait, in the presence of contributory factors, exist and we recently reported three such patients. The occurrence of retinopathy in haemoglobin C trait is even less well documented. Haemoglobin C does not cause red blood cell sickling but is known to decrease erythrocyte plasticity and increase blood viscosity. We report three cases in which haemoglobin C trait was associated with significant peripheral vascular occlusion and seafan formation (confirmed by fluorescein angiography) similar to that seen in sickle retinopathy. Two patients had coexistent systemic disease (hypertension and diabetes mellitus). Vitreous haemorrhage was the presenting feature in two patients. It is evident that haemoglobin C trait may be associated with sight-threatening complications.

Bilateral symmetrical branch retinal artery occlusions.

We present a report of a 52-year-old hypertensive patient with documented bilateral symmetrical branch retinal artery occlusions involving the maculae. The patient presented with no visual symptoms and maintained 6/5 unaided visual acuity in each eye. Although the incidence of retinal artery occlusion in hypertensive patients is well documented, symmetrical bilateral branch retinal artery occlusions suggest a possible anatomical vascular predisposition.

Sickle retinopathy in patients with sickle trait.

Sickle trait is traditionally considered a benign condition by ophthalmologists. Three cases of sickle retinopathy in subjects with sickle trait are reported. In all cases the onset of retinopathy was related to other contributing factors: in one case a traumatic hyphaema and raised intraocular pressure, in two others diabetes mellitus. Patients with sickle trait are at risk of retinopathy if coincident ocular or systemic disease is present.

Corneal perforation as a complication of epidermolysis bullosa acquisita.

Epidermolysis bullosa acquisita (EBA) is now recognised as a histopathologically distinct condition. Ocular complications of hereditary epidermolysis bullosa (EB) have been well documented, but little has been reported with respect to the ocular manifestations associated with the acquired form. A patient with EBA and sarcoidosis--an association that does not appear to have been previously reported--developed spontaneous peripheral corneal melting and perforation. The defect healed with the use of a bandage contact lens, antibiotics, mydriatics and pulsed intravenous steroids, and resulted in a satisfactory visual outcome.

Screening for ophthalmic manifestations of sickle cell disease in the United Kingdom.

There are marked variations in the manifestations of sickle disease in different populations. The ocular complications of this condition amongst the Afro-Caribbeans living in the United Kingdom have not previously been reported. We present the preliminary results of an ophthalmic screening programme at King's College Hospital, London. One hundred eyes of 50 patients with sickle cell disease were assessed. Full ocular examination was performed including fundus fluorescein angiography. We have looked at the haematological and clinical profile of the patients involved as well as the number of days spent in hospital during the year preceding the eye examination. The incidence of grade II retinopathy was found to be significantly higher than grade I in SC disease. This concurs with the results of the Jamaican screening and confirms that these patients are at higher risk of visual impairment than those with SS disease. Our results also agree with the Jamaican experience which suggest that visual morbidity is mostly due to complications of proliferative sickle retinopathy (PSR). However, the findings in patients without proliferative changes are different; in particular, angioid streaks leading to disciforms are an important cause of visual loss in Jamaica, but were not seen in any of the 98 eyes examined in this study. No correlation was found between the grade of retinopathy and age, sex, systemic complications and various haematological parameters except for the percentage of haemoglobin F, which was significantly higher in patients with grade I (7.6) compared with grade II (4.2) retinopathy (p = 0.0127).

The effect of surgery on the AC/A ratio.

The accommodative convergence/accommodation (AC/A) ratio is used clinically as a diagnostic tool in the assessment of convergence excess and near esotropia and the differentiation of true and simulated divergence excess. An abnormally high AC/A ratio has been implicated in the aetiology of some forms of strabismus but the evidence for alteration in the ratio following surgery is inconclusive. In a prospective study of 38 patients the effect of routine squint surgery was investigated in concomitant strabismus. The AC/A ratio was found to decrease significantly after surgery in both esotropes and exotropes. Furthermore a trend was demonstrated which suggested an increased risk of overcorrection in esotropes with a high (> or = 7:1) pre-operative AC/A ratio.

Screening for opthalmic manifestations of sickle cell disease in the United Kingdom

There are marked variations in the manifestations of sickle cell disease in different populations. The occular complications of this condition amongst the Afro-Caribbeans living in the United Kingdom have not previously been reported. We present the preliminary results of an opthalmic screening programme at King's College Hospital, London. One hundred eyes of 50 patients with sickle cell disease were assessed. Full ocular examination was performed including fundus fluorescein angiography. We have looked at the haemotological and clinical profile of the patients involved as well as the number of days spent in the hospital during the year preceding the examination. The incidence of Grade 11 retinopathy was found to be significantly higher than grade 1 in SC disease. This concurs with the results of the Jamaican screening and confirms that the patients are at higher risk of visual impairment than those wuth the SS disease. Our results also agrees with the Jamaican experience which suggests that visual morbidity is mostly due to complications of proliferative sickle cell retinopathy (PSR). However, the findings in patients without proliferative changes are different; in particular, angloid streaks leading to disciforms are an important cause of visual loss in Jamaica, but were not seen in any of the 98 eyes examined in this study. No correlation was found between the grade of retinopathy and age, sex, systemic complications and various haematological parameters except for the percentage of haemoglobin F, which was significantly higher in patients with grade I (7.6) compared with grade II (4.2) retinopathy (p=0.0127)(AU)

Bilateral external chalazia presenting as granulomas of the lower eyelids.

A 2-year-old oriental boy with bilateral symmetrical external chalazia is described. The diagnosis of this very unusual clinical picture became apparent only after histological examination and consultation with an eyelid specialist.

Tuberculous keratoconjunctivitis.

A 15-year-old West Indian boy had a left keratoconjunctivitis (KC) initially thought to be allergic in origin. He then developed a facial vesicular skin rash and a diagnosis of herpes simplex was suspected. Viral cultures were negative and there was a poor response to topical antiviral treatment. The KC progressed and became bilateral causing considerable reduction in the visual acuities. He complained of general fatigue and was pyrexial with generalised non-tender lymphadenopathy. There was a shadow in the upper lobe of the right lung. The bronchus was semioccluded by a non-caseating granuloma but no acid fast bacilli were found in the sputum or bronchial washings. In the presence of a strongly positive Heaf test, anti-tuberculous treatment was instituted which led to rapid resolution of all the systemic and ocular signs.