Inherited Optic Neuropathies: Real-World Experience in the Paediatric Neuro-Ophthalmology Clinic.

Inherited optic neuropathies affect around 1 in 10,000 people in England; in these conditions, vision is lost as retinal ganglion cells lose function or die (usually due to pathological variants in genes concerned with mitochondrial function). Emerging gene therapies for these conditions have emphasised the importance of early and expedient molecular diagnoses, particularly in the paediatric population. Here, we report our real-world clinical experience of such a population, exploring which children presented with the condition, how they were investigated and the time taken for a molecular diagnosis to be reached. A retrospective case-note review of paediatric inherited optic neuropathy patients (0-16 years) in the tertiary neuro-ophthalmology service at Moorfields Eye Hospital between 2016 and 2020 identified 19 patients. Their mean age was 9.3 ± 4.6 (mean ± SD) years at presentation; 68% were male, and 32% were female; and 26% had comorbidities, with diversity of ethnicity. Most patients had undergone genetic testing (95% (n = 18)), of whom 43% (n = 8) received a molecular diagnosis. On average, this took 54.8 ± 19.5 weeks from presentation. A cerebral MRI was performed in 70% (n = 14) and blood testing in 75% (n = 15) of patients as part of their workup. Continual improvement in the investigative pathways for inherited optic neuropathies will be paramount as novel therapeutics become available.

Genotypic and phenotypic characterisation of RP2- and RPGR-associated X-linked inherited retinal dystrophy, including female manifestations.

BACKGROUND: With the promise of gene replacement therapy, eligible males and females with X-linked inherited retinal dystrophy (XL-IRD) should be identified. METHODS: Retrospective observational cohort study to establish the phenotypic and genotypic spectrum of XL-IRD within New Zealand (NZ). Thirty-two probands, including 9 females, with molecularly proven XL-IRD due to RP2 or RPGR mutations, and 72 family members, of which 43 were affected, were identified from the NZ IRD Database. Comprehensive ophthalmic phenotyping, familial cosegregation, genotyping, and bioinformatics were undertaken. Main outcome measures were: RP2 and RPGR pathogenic variant spectrum, phenotype in males and females (symptoms, age of onset, visual acuity, refraction, electrophysiology, autofluorescence, retinal appearance), and genotype-phenotype correlation. RESULTS: For 32 families, 26 unique pathogenic variants were identified; in RP2 (n = 6, 21.9% of all families), RPGR exons 1-14 (n = 10, 43.75%), and RPGR-ORF15 (n = 10, 34.3%). Three RP2 and 8 RPGR exons 1-14 variants are novel, rare, and cosegregate. Thirty-one percent of carrier females were significantly affected, with 18.5% of families initially classified as autosomal dominant. Of five Polynesian families, 80% had novel disease-causing variants. One Maori family showed keratoconus segregating with an ORF15 variant. CONCLUSIONS: Significant disease was present in 31% of genetically proven female carriers, often leading to an erroneous presumption of the inheritance pattern. Pathogenic variants in 44% of the families were in exon 1-14 of RPGR, more frequent than usually described, which may inform the gene testing algorithm. Proving cosegregation in families for novel variants and identifying affected females and males translates to optimised clinical care and potential for gene therapy.

Diagnosis and treatment of idiopathic intracranial hypertension.

OBJECTIVE: To review and discuss the clinical presentation and treatment of idiopathic intracranial hypertension. DISCUSSION: Visual alterations and headache are the two main symptoms of idiopathic intracranial hypertension, although additional features including cranial nerve palsies, cognitive deficits, olfactory deficits and tinnitus are not uncommon. The headache associated with idiopathic intracranial hypertension frequently has a migrainous phenotype. The underlying cause of the disorder has not yet been elucidated. Several hypotheses have been postulated but none of them can explain the full clinical picture. Therapeutic options remain limited, focusing mainly on reduction in body weight and the reduction of CSF production with carbonic anhydrase inhibitors. CONCLUSION: The accurate diagnosis of idiopathic intracranial hypertension is essential as visual deterioration due to papilledema may be irreversible. Given its phenotypic similarity and frequent overlap with chronic migraine it is essential to consider idiopathic intracranial hypertension in the diagnostic workup of chronic headache; in particular, when considering its increasing prevalence. Understanding in detail the pathophysiological mechanisms behind the associated headache would also allow study of current and future therapeutic options in a structured way.

Superior oblique enlargement in thyroid eye disease.

PURPOSE: To determine the extent of superior oblique enlargement in thyroid eye disease (TED) by comparing the cross-sectional superior oblique areas of TED patients with those of unaffected control subjects. METHODS: The medical records of TED patients treated for strabismus from January 2005 to January 2016 were reviewed retrospectively for demographic and surgical data. The cross-sectional superior oblique area was compared to age-matched controls on high-resolution orbital computed tomography (CT) using a standardized protocol. RESULTS: A total of 46 TED patients and 18 controls were included. The mean superior oblique cross-sectional area in TED subjects was 250% larger than in controls (22.88 ± 6.64 mm2 vs 9.32 ± 1.85 mm2. The mean cross-sectional area was >3 standard deviations from the mean of the control group in 96% of TED patients. CONCLUSIONS: Superior oblique enlargement in TED may occur more frequently than generally recognized, challenging the notion that TED is primarily a disease of the rectus muscles.

Optic nerve sheath fenestration in patients with visual failure associated with vestibular schwannoma.

Background: Papilloedema and visual failure can occur as a consequence of vestibular schwannoma without evidence of hydrocephalus on imaging. Conventional treatment usually includes CSF diversion procedures. We describe here the novel use of optic nerve sheath fenestration in these patients. Methods: A case series of three patients who underwent optic nerve sheath fenestration for visual complications of vestibular schwannoma. Results: Patients A and B were both 23 year old females, with visual symptoms and papilloedema at the time of presentation with a large vestibular schwannoma. Patient A had progressive, severe visual failure despite treatment with an external ventricular drain and tumour resection. She therefore went on to have bilateral optic nerve sheath fenestration surgery, which restored central vision, improved peripheral vision and resolved papilloedema. Patient B underwent optic nerve sheath fenestration as first line surgical management for visual symptoms from a large vestibular schwannoma. This resulted in resolution of visual symptoms and papilloedema and she went on to have the lesion resected at a later date. Patient C was a 54 year old male who developed visual symptoms and papilloedema following the resection of a vestibular schwannoma. This was found to be secondary to a transverse venous sinus thrombosis and he underwent an optic nerve sheath fenestration to treat the complications of this. He also had restored vision and resolution of papilloedema. Conclusion: We demonstrate, with 3 differing cases, that optic nerve sheath fenestration can be a useful and safe treatment choice for patients with visual failure and papilloedema secondary to vestibular schwannoma.

The Value of Fusional Convergence Amplitudes in Esodeviation Surgery Without Adjustable Sutures.

PURPOSE: To explore the application of preoperative fusional convergence amplitudes in the selection of a target angle for non-adjustable suture strabismus surgery with deteriorated intermittent esotropia and diplopia. METHODS: Thirty-one consecutive cases of presumed acquired non-accommodative, deteriorated intermittent esotropia managed surgically between 2005 and 2016 were reviewed retrospectively. For each individual, a target angle (deviation angle for which surgery was based) was selected preoperatively after analysis of fusional convergence amplitudes. Outcomes in patients selected for overcorrection at 6 meters (target angle > angle in primary position at 6 meters) were compared to those who had planned surgery based on a target angle that did not exceed their measured angle (target angle ≤ angle in primary position) at 6 meters. RESULTS: All 31 patients achieved binocular single vision in primary position at both near and 6 meters without prisms, orthoptic therapy, or additional surgery at 4 to 6 months postoperatively. Greater mean correction in the target angle > angle in primary position group compared to the target angle ≤ angle in primary position group was observed, but this difference was not statistically significant (P = .57). CONCLUSIONS: Among this diagnostically specific cohort with intermittent esotropia with symptomatic diplopia and measurable binocular single vision preoperatively, targeted surgery based on an analysis of preexisting fusional convergence amplitudes had an outcome that compared favorably to that of documented adjustable suture strabismus surgery. [J Pediatr Ophthalmol Strabismus. 2018;55(6):375-381.].

Bilateral superior rectus transposition and medial rectus recession for bilateral sixth nerve palsy.

PURPOSE: To present the results of bilateral superior rectus transposition with medial rectus recession in a case of chronic bilateral sixth nerve palsy. OBSERVATION: Bilateral superior rectus transposition with medial rectus recession resulted in full correction of esotropia with resolution of horizontal diplopia, improvement in abduction, and regain of stereoacuity in our case. There was minimal limitation of adduction, with no abnormal vertical or torsional changes. CONCLUSION AND IMPORTANCE: Bilateral superior rectus transposition with medial rectus recession appears to be a useful procedure for surgical treatment of bilateral sixth nerve palsy with minimal side effects. Given its potential for reduced risk of anterior segment ischemia (ASI), it may have especially good value in the select group of patients at risk for ASI. Studies with larger sample size and longer follow up are needed to further evaluate this procedure and elucidate the variables in surgical technique for superior rectus transposition.

Retinal haemorrhage in infants with pertussis.

AIMS: It has been hypothesised that paroxysmal coughing in infantile pertussis (whooping cough) could produce retinal haemorrhages identical to those seen in abusive head trauma. We aimed to test this hypothesis. METHODS: This is a prospective study of infants hospitalised with pertussis in Auckland, New Zealand, from 2009 to 2014. The clinical severity of pertussis was categorised. All infants recruited had retinal examination through dilated pupils by the paediatric ophthalmology service using an indirect ophthalmoscope. RESULTS: Forty-eight infants with pertussis, aged 3 weeks to 7 months, were examined after a mean of 18 days of coughing. Thirty-nine had severe pertussis and nine had mild pertussis. All had paroxysmal cough, and all were still coughing at the time of examination. No retinal haemorrhages were seen. CONCLUSIONS: We found no evidence to support the hypothesis that pertussis may cause the pattern of retinal haemorrhages seen in abusive head trauma in infants.

The New Pretender: A Large UK Case Series of Retinal Injuries in Children Secondary to Handheld Lasers.

PURPOSE: To characterize a large single-center series of retinal injuries in children secondary to handheld laser devices, with emphasis on potential prognostic factors. DESIGN: Retrospective case series. METHODS: Sixteen children (24 eyes) with retinal injuries secondary to handheld lasers were identified from our electronic patient record system. Case notes, digital fundus photography, and spectral-domain optical coherence tomography images were reviewed. RESULTS: The mean age of affected children was 12.7 years (range 9-16 years), with 12 male and 4 female subjects. Mean follow up was 5.4 months (range 1-23 months). Five children (31%) were referred as suspected retinal dystrophies. The mean logMAR visual acuity at presentation was 0.30 (20/40) (range -0.20 [20/12.5] to 1.6 [20/800]). Eleven children (69%; 15 eyes) had "mild" injuries with focal retinal disruption confined to the photoreceptor and ellipsoid layers; such injuries were associated with a better prognosis, the mean visual acuity at presentation being 0.10 (20/25). "Moderate" injuries were seen in 3 eyes of 2 children, with retinal disruption confined to the outer retinal layer but diffuse rather than focal in nature. Three patients (4 eyes) had "severe" injuries, with subfoveal outer retinal architecture loss and overlying hyperreflective material in inner retinal layers. CONCLUSION: Retinal injuries secondary to handheld laser devices may be difficult to diagnose and are likely underreported. It is important that such data are in the public domain, so regulatory authorities recognize the importance of laser retinopathy as an avoidable cause of childhood visual impairment and take steps to minimize the incidence and impact of laser injuries.

Red reflex screening in New Zealand: a large survey of practices and attitudes in the Auckland region.

AIMS: Red reflex testing forms an essential part of newborn (within the first week of life) and infant (6 weeks of age) screening in New Zealand, as outlined in the Well Child/Tamariki Ora handbook. This survey of practitioners undertaking red reflex screening aimed to determine current practices and attitudes of screeners, as well as any barriers to screening. METHODS: A short, multiple-choice, on-line questionnaire was sent to approximately 1,500 health care professionals undertaking red reflex screening, over a 4-week period. RESULTS: Four hundred and eighty-three survey responses were received from 267 GPs (55.4%), 153 midwives (31.7%), and 50 paediatricians (10.4%). Thirty-six respondents (7.8%) performed red reflex screening only when they had time to do so, 13 (2.8%) only undertook this when there were concerns raised by the parents. Most respondents (97.3%) used an ophthalmoscope to perform screening. Seventynine respondents (16.6%) felt they were "not sure/underconfident" at performing this test. Only 83 of 479 respondents (17.3%) had received any formal training. CONCLUSIONS: The development of an online resource or practical 'refresher' sessions would be well received and likely to improve current practices.

Isolated inferior oblique myectomy for vertical deviations of at least 20 prism diopters in the primary position.

PURPOSE: To investigate the efficacy of inferior oblique (IO) myectomy in patients with primary position hyperdeviations ≥20(Δ), with unilateral IO overaction and clinically normal or minimally underacting superior oblique ductions, where excyclotorsion was not a barrier to fusion in primary position. METHODS: The medical records of patients who underwent IO myectomy from 1999 to 2014 were retrospectively reviewed to identify those with primary position hyperdeviations of ≥20(Δ). Postoperative changes in vertical deviations in primary position and horizontal and vertical planes were analyzed. RESULTS: A total of 17 patients were included. Mean follow-up was 17.3 months. At last follow-up, the mean hyperdeviation decreased in all five documented positions of gaze by 84% of the initial value, with mean reduction in the primary position vertical deviation from 26.5(Δ) to 4.1(Δ). There was rapid early reduction of deviation in all gaze positions (mean, 53%) at 2-4 weeks' follow-up, with a corresponding mean reduction of vertical deviation to 11.4(Δ). There were no overcorrections, but 5 patients (29%) had a postoperative primary position hyperdeviation of >5(Δ). Two patients (12%) required further vertical rectus surgery. CONCLUSIONS: In our patient cohort, isolated IO myectomy did not result in symptomatic overcorrections and had a reoperation rate that compares favorably to the traditional primary simultaneous two-muscle approach.

Relapsing-Remitting Sixth Nerve Palsy in Association with Ollier's Disease.

Relapsing-remitting sixth nerve palsy is usually due to ophthalmoplegic migraine (recurrent cranial nerve palsy) in younger patients and microvascular disease in older patients. There have been isolated reports, however, of it occurring in the presence of a skull base tumour. We report a 20-year-old woman with Ollier's disease who presented with a relapsing-remitting sixth nerve palsy. Neuro-imaging revealed a skull base enchondroma.

Auditory and visual health after ten years of exposure to metal-on-metal hip prostheses: a cross-sectional study follow up.

Case reports of patients with mal-functioning metal-on-metal hip replacement (MoMHR) prostheses suggest an association of elevated circulating metal levels with visual and auditory dysfunction. However, it is unknown if this is a cumulative exposure effect and the impact of prolonged low level exposure, relevant to the majority of patients with a well-functioning prosthesis, has not been studied. Twenty four male patients with a well-functioning MoMHR and an age and time since surgery matched group of 24 male patients with conventional total hip arthroplasty (THA) underwent clinical and electrophysiological assessment of their visual and auditory health at a mean of ten years after surgery. Median circulating cobalt and chromium concentrations were higher in patients after MoMHR versus those with THA (P<0.0001), but were within the Medicines and Healthcare Products Regulatory Agency (UK) investigation threshold. Subjective auditory tests including pure tone audiometric and speech discrimination findings were similar between groups (P>0.05). Objective assessments, including amplitude and signal-to-noise ratio of transient evoked and distortion product oto-acoustic emissions (TEOAE and DPOAE, respectively), were similar for all the frequencies tested (P>0.05). Auditory brainstem responses (ABR) and cortical evoked response audiometry (ACR) were also similar between groups (P>0.05). Ophthalmological evaluations, including self-reported visual function by visual functioning questionnaire, as well as binocular low contrast visual acuity and colour vision were similar between groups (P>0.05). Retinal nerve fibre layer thickness and macular volume measured by optical coherence tomography were also similar between groups (P>0.05). In the presence of moderately elevated metal levels associated with well-functioning implants, MoMHR exposure does not associate with clinically demonstrable visual or auditory dysfunction.

Vision and multiple sclerosis.

Multiple sclerosis can affect vision in many ways, including optic neuritis, chronic optic neuropathy, retrochiasmal visual field defects, higher order cortical processing, double vision, nystagmus and also by related ocular conditions such as uveitis. There are also side effects from recently introduced multiple sclerosis treatments that can affect vision. This review will discuss all these aspects and how they come together to cause visual symptoms. It will then focus on practical aspects of how to recognise when there is a vision problem in a multiple sclerosis patient and on what treatments are available to improve vision.

Successful use of intravitreal bevacizumab and pascal laser photocoagulation in the management of adult Coats' disease.

Traditional methods of managing exudative retinal detachment secondary to Coats' disease have been associated with varying degrees of success. We describe a case of a 34 year-old male who presented with a sub-total exudative retinal detachment of the right eye that encroached upon the macula, associated with a vasoproliferative tumor secondary to Coats' disease. The patient under-went successful treatment with two intravitreal injections of bevacizumab (Avastin, Genetech Inc., San Francisco, CA, USA) combined with targeted laser photocoagulation with a 532 nm Pascal laser (Topcon Corp., Tokyo, Japan). The visual acuity improved 5 days after the second intravitreal injection from 6/18 to 6/5, with no residual macular edema and complete regression of the vasoproliferative tumor. The improvement in visual acuity was maintained at 12 months post-treatment. We believe this is the first case report describing the successful use of Pascal laser photocoagulation with intravitreal bevacizumab in the treatment of Coats' disease. Our aim was to defer laser treatment until 'near total' retinal reattachment and regression of the vasoproliferative tumor was achieved. There are, however, reports of vitreous fibrosis in patients with Coats' disease treated with intravitreal bevacizumab. This suggests further long-term follow-up studies are required in patients treated with this approach.

Effect of superior oblique weakening on vertical alignment and horizontal and vertical incomitance in patients with A-pattern strabismus.

PURPOSE: To determine the relationship between the magnitude of preoperative A pattern and the correction of vertical alignment and horizontal and vertical incomitance in patients treated with superior oblique muscle-weakening procedures for A-pattern strabismus. METHODS: The records of consecutive patients who underwent surgery for A-pattern strabismus between 1997 and 2008 were retrospectively reviewed. Both horizontal (from up- to downgaze) and vertical (from right to left gaze) incomitance were assessed. RESULTS: Twenty-six patients were treated with superior oblique muscle-weakening procedures (either tendon spacer or nasal or posterior 7/8 temporal tenotomy, with or without simultaneous rectus muscle surgery). In these patients, the A pattern improved from 36Δ preoperatively (range, 15Δ-75Δ) to 6Δ postoperatively (range, 0Δ-16Δ). The magnitude of the reduction in A pattern correlated strongly with the size of preoperative A pattern (r=0.92), whereas the reduction in the magnitude of the vertical incomitance correlated weakly with the magnitude of the preoperative deviation (r=0.56). There was no significant correlation between the magnitude of the A pattern and the vertical incomitance (r=0.25). Of the 9 patients with preexisting primary position vertical deviation≥6Δ, 5 required additional vertical rectus muscle surgery. CONCLUSIONS: Superior oblique muscle-weakening surgery improved the A pattern but did not reliably improve the primary position vertical deviation and lateral gaze vertical incomitance. Patients with associated primary position vertical deviations of >6Δ preoperatively tended to have a greater likelihood of requiring additional strabismus surgery.