Tocilizumab use in giant cell arteritis: comparing Pharmaceutical Benefits Scheme eligible and ineligible cases in South Australia.

Tocilizumab (TCZ) is increasingly used as a steroid-sparing agent in giant cell arteritis (GCA), but there are strict Pharmaceutical Benefits Scheme (PBS) restrictions for its use in Australia. Patients who do not meet the PBS criteria can obtain TCZ through public hospital individual patient use (IPU) schemes which may not be universally accessible. We compared patients receiving IPU-approved TCZ with patients receiving PBS-subsidised TCZ and found IPU approvals were granted mainly for visual loss, a serious complication of GCA, in patients who otherwise failed to meet PBS criteria. Further studies demonstrating that TCZ is comparatively more effective than prednisolone monotherapy, as well as cost-effective, are needed to substantiate the rationale for expanding PBS approval criteria.

Optic nerve sheath infiltration in dysthyroid optic neuropathy.

PURPOSE: To assess the association of optic nerve sheath (ONS) infiltration, fat infiltration, and scleral enhancement with active thyroid eye disease (TED) and dysthyroid optic neuropathy (DON). METHODS: Thyroid eye disease patients who had axial and coronal fat-suppressed contrast enhanced T1-weighted magnetic resonance imaging (MRI) imaging performed were included. Optic nerve sheath infiltration was defined by the presence of thickening and circumferential enhancement of the optic nerve sheath. Clinical assessments were performed by orbital surgeons or neuro-ophthalmologists and the disease activity (active/inactive) and presence or absence of dysthyroid optic neuropathy were recorded. RESULTS: The study population consisted of 76 orbits from 38 patients with a mean age of 53 ± 15 years, with 25 (66%) being female. Optic nerve sheath infiltration was present in 28 (37%) orbits, fat infiltration in 37 (49%) and scleral enhancement in 14 (18%) orbits. ONS infiltration (OR 19.8, p < 0.01), fat infiltration (OR 5.2, p < 0.01) and scleral enhancement (OR 12.2, p = 0.01) were all significantly associated with active clinical disease. Patients with ONS infiltration had a significantly higher odds of dysthyroid optic neuropathy (OR 3.4, p < 0.05). Fat infiltration (OR 2.8, p = 0.1) and scleral enhancement (OR 2.3, p = 0.23) were not significantly associated with DON. CONCLUSIONS: Optic nerve sheath infiltration may be a predictor of dysthyroid optic neuropathy. Intraorbital fat infiltration and scleral enhancement may be used to detect active TED. These radiological findings may serve as useful diagnostic and stratification tools in evaluating TED patients.

The Efficacy, Adverse Effects and Economic Implications of Oral Versus Intravenous Methylprednisolone for the Treatment of Optic Neuritis: A Systematic Review.

INTRODUCTION: Optic neuritis may occur in a variety of conditions, including as a manifestation of multiple sclerosis. Despite significant research into the efficacy of corticosteroids as a first-line treatment, the optimal route of administration has not been well defined. This review aims to explore the efficacy, adverse effects and economic implications of using oral versus intravenous methylprednisolone to treat acute optic neuritis. METHODS: A systematic search of the databases PubMed/MEDLINE, Embase and CENTRAL was performed to July 2022, prior to data collection and risk of bias analysis in accordance with the PRISMA guidelines. RESULTS: Six articles fulfilled the inclusion criteria. The results showed that in the treatment of acute optic neuritis, oral methylprednisolone has a non-inferior efficacy and adverse effect profile in comparison to intravenous methylprednisolone. In a cost analysis, oral methylprednisolone to be more cost-effective than intravenous methylprednisolone. CONCLUSIONS: Oral methylprednisolone has comparable efficacy and adverse effect profiles to intravenous methylprednisolone for the treatment of optic neuritis. The analysis suggests oral administration is more cost-effective than intravenous administration; however, further analyses of the formal cost-benefit ratio are required.

Distinguishing laboratory characteristics in giant cell arteritis: a real-world retrospective cohort study.

BACKGROUND: Untreated Giant Cell Arteritis (GCA) has the potential to cause serious complications such as vision loss. Appropriate initial assessment by General Practitioners, early treatment and specialist referral are therefore essential in reducing morbidity. However, lack of awareness around the range of presentations can lead to a delay in diagnosis. OBJECTIVE: We aim to evaluate the discriminative diagnostic performance of laboratory characteristics associated with GCA in our population over a period of 18 months. DISCUSSION: This is a real-world retrospective review of patients referred to ophthalmology services with concern for GCA. The pre-test probability of a patient referred with suspected GCA was 13.9% to have GCA, highlighting the need for specialist referrals to continue. White Cell Count (p = 0.01), Platelet Count (p = 0.02), Erythrocyte sedimentation rate (p = 0.004) and C-reactive protein (p = 0.002) were significantly different between GCA and non-GCA cases. Moreover, this study demonstrates that absolute neutrophil count (p = 0.02) can be a useful parameter in initial investigations for GCA.

A review of patient-reported outcome measures used in uveitis.

We review patient-reported outcome measures (PROMs) used to evaluate the quality of life (QoL) in uveitis and provide a quality assessment of the psychometric properties of the PROMs, making it easier to choose the best questionnaire for uveitis. Our review included 158 articles. A total of 98 PROMs were used to measure QoL in uveitis and the National Eye Institute Visual Function Questionnaire 25 (NEI VFQ -25) was the most frequently used PROM in these studies. There were 5 uveitis-specific PROMs, but they were meant for either birdshot choroidopathy or cytomegalovirus retinitis or paediatric uveitis. There are no PROMs developed explicitly for the more common, anterior uveitis, intermediate uveitis, panuveitis, and chronic uveitis. The uveitis-specific PROMs performed better in our quality assessment criteria compared to other PROMs. However, these PROMs were constructed using traditional classical test theory and have not been assessed using the modern family of psychometric assessment methods such as Rasch analysis. As new therapeutic modalities for uveitis such as the new biological agents and steroid implants, continue to evolve, a comprehensive PROM will be increasingly valued in clinical trial settings to compare the effects of treatments from the patient's perspective.

The Role of Tocilizumab in Glucocorticoid Resistant Giant Cell Arteritis: A Case Series and Literature Review.

BACKGROUND: Glucocorticoid-resistant giant cell arteritis (GCA) describes a subgroup of patients whose visual acuity further declines despite immediate administration of high-dose intravenous glucocorticoids. Tocilizumab, a recombinant humanized anti-interleukin-6 receptor monoclonal antibody may be used as "rescue" therapy in these cases but requires more research. METHODS: We present a literature review on tocilizumab as rescue therapy and a retrospective case series of 5 consecutive glucocorticoid (GC) resistant, temporal artery biopsy (TAB)-positive [corrected] patients. RESULTS: The use of tocilizumab as rescue therapy for GC-resistant GCA is limited to 3 case reports. Two cases saw visual acuity improvement in the newly affected contralateral eye after 8 mg/kg of intravenous tocilizumab (from 6/60 to 6/15 in one case and hand motion to 6/6 in another). The third described stabilization and prevention of further best-corrected visual acuity (BCVA) decline. All 5 of our patients presented with acute monocular vision loss. BCVA ranged from 6/12 to light perception (LP). All patients were promptly commenced on 1 g intravenous methylprednisolone daily. Weekly 162 mg of subcutaneous tocilizumab was commenced once contralateral eye involvement was noted. Tocilizumab resulted in bilateral BCVA gains in 2 cases, recovery of the contralateral eye in one, and no effect in the remaining 2 cases. BCVA recovery was no light perception to 6/6 after 6 weeks of tocilizumab. Tocilizumab had no effect in cases with severe vision loss and high C-reactive protein on presentation. CONCLUSIONS: We agree with existing hypothesis that tocilizumab likely prevents a "pending" central retinal artery occlusion by maintaining retinal vasculature perfusion. Our case series suggests that there is a role for tocilizumab as "rescue" therapy for GC-resistant GCA, where vision loss would otherwise be imminent.

Calciphylaxis, beware the ophthalmic mimic: A case series.

PURPOSE: We present two atypical cases of calciphylaxis presenting with ocular ischemic pathology - both without the hallmark cutaneous manifestations - to raise awareness of this rare yet highly disabling condition. OBSERVATIONS: We report two cases of ophthalmic calciphylaxis presenting as (1) anterior ischemic optic neuropathy (AION) and cilioretinal artery occlusion in a 76-year-old woman with pre-dialysis kidney failure, and (2) AION with contralateral central retinal artery occlusion (CRAO) in a 44-year-old man on hemodialysis. CONCLUSION AND IMPORTANCE: These cases highlight the need for judicious clinical suspicion of calciphylaxis in patients with kidney failure, presenting with microvascular ischemic ophthalmic pathology such as AION or CRAO. Confirmation with temporal artery biopsy is essential to direct targeted individualized multi-disciplinary treatment of calciphylaxis and avoid unnecessary steroid exposure in cases masquerading as giant cell arteritis (GCA).

Pallid Disc Oedema in a Young Patient: Clinical and Diagnostic Challenge.

A mid-thirties male with end-stage renal failure receiving haemodialysis on a background of four failed renal transplants, post-transplant lymphoproliferative disorder,and autonomic dysfunction presented with acute vision change in his left eye. Over days his vision in that eye deteriorated from 20/25 to no light perception. Given his complex medical background he was extensively investigated for infective, inflammatory, infiltrative and vasculitic aetiologies to explain acute vision loss with pallid disc swelling. A final diagnosis of non-arteritic anterior ischaemic optic neuropathy secondary to refractive hypotension and haemodialysis was reached.

Optic neuropathy secondary to perhexiline and amiodarone.

Bilateral optic disc swelling is an important clinical sign for potentially life-threatening and sight-threatening conditions, with the most common being raised intracranial pressure and pseudopapillitis. Perhexiline-related and amiodarone-related optic disc swellings are diagnoses of exclusion. This report describes the diagnosis of a man with perhexiline-induced and amiodarone-induced optic neuropathy after extensive investigation consisting of full ophthalmic examination, biochemical screen, temporal artery biopsy, CT, MRI, positron emission tomography and lumbar puncture. There was partial to complete resolution of optic neuropathy following cessation of the causative medication. We postulate that the underlying mechanism of perhexiline toxicity could be mitochondrial dysfunction related. Our case demonstrates that patients treated with perhexiline and amiodarone should be monitored closely for ocular side effects.

Diagnosis and management of giant cell arteritis: Major review.

Giant cell arteritis is a medical emergency because of the high risk of irreversible blindness and cerebrovascular accidents. While elevated inflammatory markers, temporal artery biopsy and modern imaging modalities are useful diagnostic aids, thorough history taking and clinical acumen still remain key elements in establishing a timely diagnosis. Glucocorticoids are the cornerstone of treatment but are associated with high relapse rates and side effects. Targeted biologic agents may open up new treatment approaches in the future.

Vogt-Koyanagi-Harada syndrome presenting with bilateral optic disc swelling and leptomeningeal enhancement.

Vogt-Koynagi-Harada (VKH) disease is a clinical syndrome with classical ocular and extraocular findings that is not uncommonly described in Asian, Middle-Eastern and South American populations. We describe a case of VKH in an elderly Polish-Australian distinguished by prominent bilateral disc swelling rather than uveitis and marked leptomeningeal enhancement on MRI which led to extensive investigation including brain biopsy. Both disc oedema and MRI abnormalities improved dramatically with systemic steroid therapy. VKH disease is an important differential to consider in older patients with an uveo-meningeal picture and atypical eye findings where other causes have been excluded.

Understanding quality of life impact in people with retinal vein occlusion: a qualitative inquiry.

BACKGROUND: Although being the second most common sight-threatening retinal vascular disease after diabetic retinopathy, the patient-centred impact of retinal vein occlusion has not been well studied. This study aims to understand the quality of life issues in people with retinal vein occlusion using a qualitative methodology. METHODS: In-depth semi-structured interviews were conducted with 17 patients with retinal vein occlusion. All the interviews were digitally recorded and transcribed verbatim. An inductive analytic approach based on the constant comparative method was used for coding, aggregation, and theme development. The qualitative analysis was done using the software NVivo. RESULTS: Participants had a median age of 73 years (range 34-85 years; females, 71 per cent). Six quality of life themes were identified: concerns about the disease progression and treatment outcome (health concerns), emotional responses to the disease (emotional), experiencing a range of symptoms (symptoms), inability to do things as before (activity limitation), adapting to the visual loss (coping), and inconveniences due to the eye condition (convenience). Participants often felt that lasers and injections did not improve their vision. They feared that their eye condition may come back, or the other eye may be affected. They experienced a range of visual symptoms that affected their day-to-day performance, particularly reading small print, and driving at night. Having multiple treatments and frequent eye appointments were major sources of inconvenience. Patients adopted several coping strategies to manage the stress associated with visual loss. CONCLUSIONS: This study shows that several aspects of quality of life are compromised in people with retinal vein occlusion. The findings of this study will be used to identify the item content for a vitreoretinal disease-specific quality of life item bank.

Acute hypertensive uveitis as the first presentation of multiple sclerosis.

Ophthalmic manifestations of multiple sclerosis are frequent including acute optic neuritis, ocular motor disturbances and intermediate uveitis. We report an unusual case of multiple sclerosis presenting as acute hypertensive uveitis. A 56-year-old man was referred by his family doctor with a 2-week history of right eye pain and decreased vision. Best-corrected visual acuity was Count Fingers on the right and 6/9-2 on the left. Intraocular pressure was 55mmHg and 14 mmHg on the right and left respectively. He had a right relative pupillary defect and a left internuclear ophthalmoplegia. Vitreous cells were present in the right eye and there was peripheral sclerosis and periphlebitis superior temporally. MRI Brain and Spine revealed multiple T2 hyperintense lesions consistent with multiple sclerosis. Multiple sclerosis may present initially with an acute elevation of intraocular pressure and intermediate uveitis.

A case of traumatic infraorbital neuroma.

A 53-year-old Afghan man presented with a 12-month history of left proptosis, diplopia and facial swelling 20 years after a bomb blast injury. Magnetic resonance and computed tomography imaging revealed a well-circumscribed lesion centred within the left inferior orbit/superior maxillary sinus along with left orbital fracture. Histopathology and immunostaining of the debulked lesion were consistent with traumatic neuroma of the infraorbital nerve. Infraorbital neuromas have developed following orbital decompression surgeries but have not been reported previously following non-surgical trauma.

Exploring the quality of life issues in people with retinal diseases: a qualitative study.

BACKGROUND: The lack of an appropriate retina-specific patient-reported outcome instrument restricts the understanding of the full impact of hereditary retinal diseases and other less common but potentially blinding acquired retinal diseases such as, vascular occlusions, epiretinal membrane, macular hole, central serous retinopathy and other vitreoretinopathies on quality of life. This study aims to explore the quality of life issues in people with hereditary retinal diseases and acquired retinal diseases to develop disease-specific patient-reported outcome instruments. METHODS: A qualitative research methodology to understand the lived experiences of people with retinal diseases was carried out. Data were collected through semistructured interviews. The coding, aggregation and theme development was carried out using the NVivo -10 software. RESULTS: Seventy-nine interviews were conducted with participants with hereditary retinal diseases (n = 32; median age = 57 years) and acquired retinal diseases (n = 47; median age = 73 years). We identified nine quality of life themes (domains) relevant to people with retinal diseases. Difficulty in performing important day-to-day activities (activity limitation) was the most prominent quality of life issue in the hereditary retinal diseases group whereas concerns about health, disease outcome and personal safety (health concerns) was the most prominent quality of life issue in the acquired retinal diseases group. Participants with hereditary retinal diseases had more issues with social interaction (social well-being), problems with mobility and orientation (mobility), and effect on work and finance (economic) than participants with acquired retinal diseases. On the contrary, participants with acquired retinal diseases reported more inconveniences (conveniences) than participants with hereditary retinal diseases, which were mostly attributed to treatment. Participants with hereditary retinal diseases were coping better compared to participants with acquired retinal diseases. CONCLUSIONS: Our study found that participants with both hereditary and acquired retinal diseases are living with myriad of disease-specific quality of life issues. Many of these issues are completely different and unique to each disease group. Hence, these group of diseases would need separate patient-reported outcome instruments to capture the disease-specific quality of life impacts.

Frosted branch angiitis in an octogenarian with infective endocarditis.

PURPOSE: To present the difficulties in diagnosing frosted branch angiitis (FBA) in an elderly person, and to present the likely immunogenic association of FBA with alpha-hemolytic streptococci. METHODS: Thorough review of the medical records of an 80-year-old white man diagnosed with FBA. Patient consent was obtained before the writing of this article. RESULTS: Our patient presented with 1 week of decreasing vision and floaters in his right eye and 3 days of floaters in his left eye. Significant medical history included a prosthetic mitral valve. Notable features on examination were bilateral retinal vascular sheathing, with retinal edema and hemorrhage. Preliminary investigations-including a transoesophageal echocardiogram-did not reveal intraocular or systemic infection, autoimmune disease, or underlying malignancy. Idiopathic FBA was unlikely given that the majority of cases had been documented in middle-aged Japanese populations. Thus, we chose to treat our patient empirically for common causes of retinal vasculitis such as viral retinitis. Interestingly, 2 weeks after the diagnosis of FBA, our patient became febrile. He was subsequently diagnosed with infective endocarditis and commenced on intravenous vancomycin (penicillin allergy). Review of his transoesophageal echocardiogram found an oscillating lesion that had been initially missed. Therefore, it is likely that our patient had blood culture-negative endocarditis at the time of presentation. This was further supported by the regression of his ocular disease with intravenous vancomycin. CONCLUSION: We hypothesize that our patient developed FBA as an immunogenic response to Streptococcus viridans and Streptococcus oralis infection. Previous associations between streptococci and FBA have been made. Notably, beta-hemolytic streptococcal antigens are known to cross-react with retinal antigens. However, the implicated pathogens in our patient were alpha-hemolytic. Alpha-hemolytic streptococcal endophthalmitis has been linked to frosted branch response before, but it has never been associated with FBA through an immunogenic pathway. Therefore, it is important to note that idiopathic FBA can be associated with infective endocarditis and alpha-hemolytic streptococcal infections. Furthermore, FBA in elderly patients needs thorough evaluation to rule out systemic causes.