Successful Late Treatment of Orbital Infantile Haemangiomas in Two Teenagers with Topical Transcutaneous Timolol Maleate 0.5% Alone.

We previously described the first successful treatment of deep periocular and, subsequently, orbital infantile haemangiomas (IH) with topical transcutaneous timolol maleate 0.5% (TM 0.5%) alone as the first-line treatment in the acute proliferative phase in infancy. It is not known whether orbital IH with persistent proptosis in later years, untreated in infancy, would still respond to TM 0.5% treatment as well. To our best knowledge, we here present the first reports of the successful late treatment of persistent orbital IH with topical timolol maleate 0.5% applied to the skin overlying the orbital IH in two teenagers. Case 1 was an 11-year-old girl with proptosis measuring 4 mm before and 7 mm after Valsalva manoeuvre that diminished to 1 mm after topical treatment. Case 2 was a 10-year-old girl with 2 mm (before) and 4 mm proptosis (after Valsalva) that decreased to 0 mm proptosis with topical treatment. The time to resolution was 19 months (case 1) and 13 months (case 2). The treatment dose was 3 drops of TM 0.5% applied an average of 1.94 (case 1) and two times daily (case 2). In comparison to proptosis, resolution of periorbital swelling required less treatment time. There was no recurrence of either proptosis or periorbital swelling 1 year after stopping treatment in either case. The findings indicate that beta-blockers are effective not just in the proliferative but also in the late involutional phase in older children. No adverse clinical effects were noted throughout treatment in either case. The presence of increased proptosis with a Valsalva manoeuvre predicts a significant persistent vascular compartment in the orbital IH and may thus serve as a simple predictive clinical sign of likely treatment success. We recommend that a trial with this well-tolerated treatment form is considered in persistent cases of orbital IH, especially in the presence of enhanced proptosis with a Valsalva manoeuvre.

Topical Timolol for Infantile Haemangioma of the Orbit.

Infantile haemangiomas (IHs) are the most common benign tumours of the eyelid and orbits in infancy. Beta-blockers, in the form of oral propranolol, have become first-line treatment in severe cases with functionally significant or disfiguring IH. However, adverse drug reactions of oral propranolol in infants are reported in 1 in 11 and serious or potentially life-threatening systemic side effects in 1 in 38, including dyspnoea, hypotension, hyperkalaemia, hypoglycaemia, and cyanosis, therefore requiring careful and close monitoring during the course of systemic treatment. More recently, two large meta-analyses have shown topical beta-blockers, such as timolol maleate 0.5%, to be as effective as oral propranolol in superficial IH, but with no or significantly fewer adverse effects, and have advocated that topical beta-blockers replace oral propranolol as the first-line treatment of superficial IH. We have previously reported the therapeutic response of deep periocular IH to primary topical timolol maleate 0.5% monotherapy. Here we also describe the first successful treatments of large orbital IHs with primary topical timolol maleate 0.5% monotherapy in four infants, resulting in immediate cessation of progression and rapid clinical improvement or resolution in all cases. No adverse effects and no recurrence during long-term follow-up of up to 2.5 years after cessation were seen in any of the patients treated with topical timolol maleate 0.5%.

Comparison of a manometric tear duct irrigation test with dacryoscintigraphy in the investigation of epiphora.

PURPOSE: Assessment of lacrimal resistance in patients with patent lacrimal systems is important in determining whether dacryocystorhinostomy (DCR) surgery is appropriate. Current techniques, including lacrimal syringing and dacryoscintigraphy (DSG), can be unreliable. We compare the results of a manometric tear duct test (mTDT) irrigation technique with DSG in these patients. METHODS: All symptomatic patients in a specialist lacrimal clinic had full work-up apart from syringing. Lacrimal resistance was assessed using mTDT which applies a fixed head of fluid pressure via a cannula sealed to punctum. Conventional syringing was also performed in cases with abnormal mTDT. Symptomatic patients with delayed tear clearance, no external cause for watering and patent lacrimal systems had DSG. MTDT and DSG results were compared, including in asymptomatic fellow eyes. RESULTS: 105 tear ducts were examined, 85 symptomatic. Symptomatic eyes had a significantly higher mean mTDT resistance (p = .0003) and more had abnormal mTDT (52%) compared to asymptomatic eyes (10%). Although mean tear duct resistance was higher in those with nasolacrimal duct stenosis (NLDS) than freely patent (FP) on syringing (8.5 vs 10.8 dpm), this was not significant (p = .6). High proportions of both FP and NLDS groups had no flow at all on mTDT (60% and 53%, respectively). DSG showed no significant difference in the symptomatic versus asymptomatic eyes (p = .36), nor between those with a normal or abnormal mTDT (p = .25), nor between FP and NLDS groups (p = .25). CONCLUSIONS: In contrast to DSG, the mTDT provides valuable, objective information on lacrimal resistance that can guide a decision to DCR surgery.

Early low-dose rituximab for active thyroid eye disease: An effective and well-tolerated treatment.

BACKGROUND: Thyroid eye disease (TED) is an autoimmune inflammatory disease that can be disfiguring and potentially sight threatening. Suppression of inflammation in active disease can reduce the risk of visual loss and limit long-term sequelae. Current management involves inflammation suppression using glucocorticoids. The aim of this study was to evaluate the efficacy of early disease intervention with targeted immunomodulatory therapy to alter disease course. This paper reports the efficacy of low-dose rituximab in reducing clinical activity in TED in a small population. METHODS: A retrospective audit of consecutive patients with active TED managed primarily with a 100 mg rituximab infusion. Further glucocorticoid or steroid-sparing agents were prescribed if clinically indicated. Clinical activity score, VISA overall severity score and Oxford Quality of Life score were recorded at each visit as well as TSH receptor antibody levels (TRAb), B cell subsets and adverse reactions. RESULTS: Twelve patients had mean follow-up of 6.3 months. Clinical activity scores significantly decreased (mean score 5.08 to 1.58; P < 0.001), VISA overall severity scores reduced by 50% from 12 to 6, P < 0.001 and the mean cumulative dose of IV methylprednisolone was 2.3 g. 100 mg rituximab induced significant CD19+ B cell depletion (n = 8, P < 0.001). There was no significant reduction in serum TRAb (n = 8, P = 0.06). A transient infusion-related rash was the only adverse effect, n = 4. QoL scores did not differ markedly before and after treatment. CONCLUSION: Low-dose rituximab is an efficacious, well-tolerated and safe treatment for active TED; reducing disease activity and allowing reduced administration of systemic steroid.

Neurofibromatosis Type 2-Related Eye Disease Correlated With Genetic Severity Type.

OBJECTIVE: Neurofibromatosis type 2 (NF2) is an uncommon but well-recognized disorder characterized by multiple schwannomas and meningiomas. Adults typically present with hearing loss and balance disturbance, and children with ocular, dermatological, and neurological signs. Clinical diagnosis is confirmed by neuroimaging and genetic testing. Although ophthalmic features are present in patients with NF2, there are no reports correlating genetic severity subtypes with ophthalmic involvement. METHODS: We retrospectively reviewed longitudinal ophthalmological data of 83 patients with NF2, with known genetic severity subtype, to determine visual function over time. We created a scoring system (Oxford NF2 Ophthalmic Score [ONOS]) to quantify visually debilitating pathology. RESULTS: The prevalence of optic atrophy, combined hamartomas, cataract, and epiretinal membranes significantly increased with genetic severity. Median age of survival to visual acuity worse than 1.0 logarithm of minimum angle of resolution in one eye significantly decreased with genetic severity and was 38 years in the genetically severe group, 49 years in moderate classics, 64 years in mild classics, and 84 years in the tissue mosaics. In the genetically severe, the visually damaging pathologies were largely untreatable. The ONOS correlated with genetic severity longitudinally and cross-sectionally. CONCLUSIONS: Mutations associated with severe systemic disease result in greater visual morbidity at an earlier age. Those with tissue mosaicism are unlikely to have visually debilitating pathology secondary to NF2. Potentially treatable sources of damage to vision, however, affect all groups and must be identified early and treated effectively to retain useful vision throughout life.

Early use of steroid-sparing agents in the inactivation of moderate-to-severe active thyroid eye disease: a step-down approach.

OBJECTIVES: The current first-line treatment for management of active thyroid eye disease (TED) is high-dose intravenous corticosteroids, which have the potential for serious adverse effects. Our aim was to evaluate the effect of steroid-sparing agents (SSAs) in patients with moderate-to-severe active TED, using methotrexate as first-line. METHODS: Presented is a retrospective, four-year, single-centre, consecutive case series of patients with moderate-to-severe TED treated using the Oxford protocol. Treatment modality, disease activity, and adverse effects are reported at presentation, 6- and 12-month follow-up. RESULTS: 104 consecutive TED patients treated by the Oxford TED team were reviewed. 24 patients with moderate-to-severe active disease were identified (mean age 46.8 years;12 female) with a mean pretreatment VISA inflammatory index score of 5.5/10 (SD = 1.98; range 1-9). Intravenous methyl-prednisolone (IVMP) and an SSA was commenced in all patients. Mean total steroid dose was 2.72 g (SD = 1.4;1.0-6.9). 38% of patients (n = 9) received ≤1.5 g of IVMP. Only two patients required >4.5 g of IVMP equating to the EUGOGO treatment protocol dose for this patient group. There was significant improvement in inflammatory index score both at the intermediate review (mean score 2.7; SD = 2.8; P < 0.001; mean follow up 25.2 weeks) and at one year or last follow-up (mean score 1.4; SD = 1.5; P < 0.001; mean follow up 48.0 weeks). No serious or long-term adverse effects were reported. CONCLUSION: This study suggests that the initiation of an SSA, using methotrexate as first-line, with limited adjuvant IVMP is an effective and safe treatment for moderate-to-severely active TED, resulting in a significant reduction in both disease activity and total steroid load.

Acute Sickle Cell Orbitopathy Masquerading as Orbital Cellulitis.

Sickle cell orbitopathy is a rare manifestation of a sickle cell crisis and can closely mimic orbital cellulitis, both clinically and radiologically. We present a case where a child presented with what was thought to be orbital cellulitis and was treated accordingly. Subtle radiologic features of sickle cell orbitopathy were initially overlooked, resulting in an incorrect diagnosis and a treatment delay for the patient. Correctly treated most cases resolve with no adverse affects, highlighting how important it is to consider acute sickle cell orbitopathy in the differential diagnosis of acute periorbital swelling in children with sickle disease.

Assessment of lacrimal resistance using a manometric tear duct irrigation system.

Lacrimal surgery aims to provide a low-resistance tear drainage passage. An assessment of lacrimal resistance guides decisions on surgery. We present results of a modified tear duct irrigation system that reliably measures lacrimal outflow resistance. Patients in a specialist lacrimal clinic had a full work-up to the point of tear duct syringing. The tear ducts were irrigated using a manometric system, which applied a fixed, known head of fluid pressure to a lacrimal cannula. Fluid flow is recorded and the lacrimal resistance derived as fluid pressure/fluid flow (units cmH20 secml-1, for simplicity presented as drops per minute, dpm). Patient groups were: A: Asymptomatic, A1: subgroup where the fellow symptomatic eye had a visible cause for watering, B: external visible cause for watering (ocular surface/lid/punctum), C: no externally visible cause, D: post op DCR, E: post syringing and probing, F: mixed/other. 444 tear ducts were examined. Mean flows (dpm) were: A1 (n = 19) 55; B (n = 183) 46; C (n = 142) 22: D (n = 38) 52. Excluding complete obstruction (n = 29), tear duct syringing only detected 48% of those with impaired manometric flow. Of those with a normal tear duct syringing, 53% had impaired manometric flow; 34% had a flow of 0 dpm. Differences in A1 versus C; B versus C and pre versus post dacryocystorhinostomy were all statistically significant (p < 0.05). The manometric system presented reliably measures lacrimal resistance and provides a substantial increase in sensitivity and specificity over conventional lacrimal syringing.

Paediatric orbital lymphoma; a case series and review of the literature.

OBJECTIVE: To describe a series of paediatric orbital lymphoma patients in a single tertiary referral centre. METHODS: A retrospective case-note search in the Oxford Eye Hospital of all patients under the age of 18 years with orbital lymphoma between 2010 and 2020. Demographic and clinical data were obtained, and a literature review was conducted. RESULTS: Five patients were identified with orbital lymphoma, mean age 48.2 ± 36 months (1-109 months), three were males. Clinical presentation included: ptosis, proptosis, lethargy, visual loss, and strabismus. Two patients had bilateral orbital disease and one patient was diagnosed within the first month of life. The tissue diagnosis revealed four cases of Burkitt's lymphoma and one case of T- lymphoblastic lymphoma. Central nervous system (CNS) sampling was also positive in the four cases of Burkitt's lymphoma. All patients were treated systemically for the lymphoma with chemotherapy. Complete remission was achieved in all cases post chemotherapy. Follow-up of 36.4 ± 18.9 months (10-61 months). CONCLUSION: This is the largest published case series of paediatric orbital lymphoma. We described a patient diagnosed within the first month of life and we believe this to have developed intra-uterine. In this series, patients were younger, had more bilateral disease and had better outcome than previously described. This rare condition should be considered in any child with an orbital mass, at any age. When managed appropriately, good outcomes can be achieved.

Early and Late Histological and Ultrastructural Findings in Resected Infantile Capillary Hemangiomas Following Treatment with Topical Beta-Blocker Timolol Maleate 0.5.

BACKGROUND: Infantile capillary hemangiomas (IHs) affect approximately 4-5% of infants. The systemic nonselective ß-adrenergic antagonist, propranolol, has become the standard first-line treatment for severe IHs. The topical ß-antagonist, timolol maleate, has also demonstrated efficacy and safety in treating superficial and some deep capillary hemangiomas. Despite their therapeutic success and prevalent use, the mechanism of action of ß-adrenergic antagonists in the treatment of IHs is not well understood. METHODS: Histopathological and electron microscopic evaluation of two periocular IHs excised at 1 week and 24 months following topical timolol treatment was performed. RESULTS: Distinct morphological differences were observed between spontaneously regressed and ß-antagonist-treated IHs. The former was characterized by diffuse collagen deposition and interstitial fibrosis, while the latter showed organized concentric collagen IV deposition within obliterated vessel lumen, suggestive of waves of endothelial cell apoptosis, leaving behind layers of basement membrane deposits as a stress response. CONCLUSIONS: Based on these observations, we hypothesize that, apart from their well-known cardiac and vasodilatory effects, ß-antagonists could induce endothelial cell apoptosis in IH leading to endovascular occlusion and we present supporting evidence to explain why this response might be specific to hypoxic tissue.

Integrating retinal simulation with a peer-assessed group OSCE format to teach direct ophthalmoscopy.

OBJECTIVE: To describe the conception and evaluation of a novel educational intervention to teach direct ophthalmoscopy with retinal simulators using a peer-assessed group objective structured clinical examination (OSCE) format. DESIGN: Prospective, single-centre educational trial at Oxford University Medical School, Oxford, U.K. PARTICIPANTS: A total of 160 consecutive undergraduate fifth-year medical students participated in the study. METHODS: Students identified prior experience, teaching, examination, and feedback relevant to direct ophthalmoscopy. Students self-evaluated their perceived confidence across 6 domains of direct ophthalmoscopy examination before and after the educational intervention using a Likert-type psychometric scale. Wilcoxon matched pair testing was used to determine statistical significance for each domain. RESULTS: The group OSCE intervention increased confidence in direct ophthalmoscopy overall from 2.5% to 63.8% (p < 0.001). Confidence improved in all 6 domains, most significantly in controls of ophthalmoscope (p < 0.001) and sequence of examination (p < 0.001) but also in the identification and interpretation of retinal signs (p < 0.001). Students rated the tutorial as very effective or effective across all 6 domains, and 96.29% rated the tutorial as effective overall. CONCLUSIONS: Retinal simulation, integrated with a peer-assessed group OSCE format, is effective in increasing confidence in all aspects of direct ophthalmoscopy. It may be insufficient alone for training in the identification and interpretation of posterior segment clinical signs. Diminishing ophthalmology clerkships worldwide require ophthalmologists to identify innovative teaching methods, using modern technology and pedagogy to deliver high-quality, yet high-throughput, training in direct ophthalmoscopy. This novel teaching strategy may be considered by ophthalmologists responsible for direct ophthalmoscopy training in a teaching hospital context.

Neisseria meningitidis endogenous endophthalmitis with meningitis in an immunocompetent child.

Neisseria meningitidis is a major cause of childhood morbidity and mortality worldwide. We describe an exceptional case of an immunocompetent 15-month-old child presenting with a unilateral anterior uveitis, hypopyon, and sepsis. Anterior chamber aspirate demonstrated gram-negative cocci before Neisseria meningitidis was identified in blood and cerebrospinal fluid. Meningococcal endophthalmitis presents variably with sepsis, meningitis, or isolated ocular symptoms. Diagnosis is a clinical challenge, requiring diagnostic sampling and treatment from both pediatricians and ophthalmologists. Delayed or incorrect treatment risks blindness, disability, or death. Simultaneous invasion of meningococcus across intact blood-brain and blood-ocular barriers in this child suggests antigenic correlates between meningeal and ocular endothelial interfaces. Meningococcus is an exclusively human pathogen; research is hampered by the lack of animal models. This clinical observation suggests the potential of a novel in vitro experimental approach of using ocular tissue from eye banks to further elucidate the meningococcal-endothelial interaction that underpins meningococcal disease.

Serial 3-dimensional computed tomography and a novel method of volumetric analysis for the evaluation of the osteo-odonto-keratoprosthesis.

PURPOSE: To assess the use of serial computed tomography (CT) in the detection of osteo-odonto-lamina resorption in osteo-odonto-keratoprosthesis (OOKP) and to investigate the use of new volumetric software, Advanced Lung Analysis software (3D-ALA; GE Healthcare), for detecting changes in OOKP laminar volume. METHODS: A retrospective assessment of the radiological databases and hospital records was performed for 22 OOKP patients treated at the National OOKP referral center in Brighton, United Kingdom. Three-dimensional surface reconstructions of the OOKP laminae were performed using stored CT data. For the 2-dimensional linear analysis, the linear dimensions of the reconstructed laminae were measured, compared with original measurements taken at the time of surgery, and then assigned a CT grade based on a predetermined resorption grading scale. The volumetric analysis involved calculating the laminar volumes using 3D-ALA. The effectiveness of 2-dimensional linear analysis, volumetric analysis, and clinical examination in detecting laminar resorption was compared. RESULTS: The mean change in laminar volume between the first and second scans was -6.67% (range, +10.13% to -24.86%). CT grades assigned to patients based on laminar dimension measurements remained the same, despite significant changes in laminar volumes. Clinical examination failed to identify 60% of patients who were found to have resorption on volumetric analysis. CONCLUSIONS: Currently, the detection of laminar resorption relies on clinical examination and the measurement of laminar dimensions on the 2- and 3-dimensional radiological images. Laminar volume measurement is a useful new addition to the armamentarium. It provides an objective tool that allows for a precise and reproducible assessment of laminar resorption.