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.

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.

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.

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.

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.

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.

Cervical carcinoma manifesting as progressive bilateral visual loss.

We report a patient with bilateral choroidal metastasis from disseminated cervical squamous cell carcinoma. A 52-year-old woman presented with progressive bilateral visual loss due to choroidal masses in both eyes. The fundus examination revealed posterior serous retinal detachment in both eyes associated with creamy choroidal lesions. A thorough systemic work-up revealed choroidal metastasis from a squamous cell carcinoma of the cervix. This case highlights the importance of a thorough systemic evaluation in patients with choroidal tumours.

Flashes and floaters - a practical approach to assessment and management.

BACKGROUND: Flashes and floaters are common ophthalmic issues for which patients may initially present to their general practitioner. It may be a sign of benign, age-related changes of the vitreous or more serious retinal detachment. OBJECTIVE: This article provides a guide to the assessment and management of a patient presenting with flashes and floaters. DISCUSSION: Although most patients presenting with flashes and floaters have benign age-related changes, they must be referred to an ophthalmologist to rule out sight-threatening conditions. Key examination features include the nature of the flashes and floaters, whether one or both eyes are affected and changes in visual acuity or visual field.

Tissue remodeling in a surgically repaired macular hole.

PURPOSE: The authors report a case with early reopening, spontaneous closure, and delayed reopening with optical coherence tomography after successful repair to highlight the dynamic nature of tissue remodeling in surgically repaired macular holes. METHOD: Observational case report. RESULT: A 62-year-old woman underwent successful surgery for Grade IV macular hole. Five weeks postoperatively, the macular hole reopened but underwent spontaneous closure at 6 months of follow-up. Nine months later, there was reopening of the macular hole, which was surgically repaired. CONCLUSION: Successful macular hole repair warrants long-term observation due to the ongoing tissue remodeling.

Neuro-ophthalmic manifestations and outcomes of pituitary apoplexy--a life and sight-threatening emergency.

OBJECTIVE: To report the neuro-ophthalmic manifestations and outcomes in patients with pituitary apoplexy. METHOD: Retrospective chart review. RESULTS: 23 patients were identified (17 men, mean age 54.1 years (range 23-86 years). The onset was abrupt in 22 patients; one patient had a subclinical presentation. Headache was the commonest presenting symptom (82.6%, 19/23). Neuro-ophthalmic manifestations were present in more than three-quarters of the patients (82.6%, 19/23). At presentation, 55 % (11/20), 47.6 % (10/21) and 60.9 % (14/23) of the patients had reduced visual acuity, field defects and cranial nerve palsies respectively. Management was conservative in 4 patients and surgical in 18 patients; one patient died shortly after presentation. The median follow up period was 10.5 months (22 patients, range 0.2-168 months). At final follow up, improvement was present in 100% of the patients with reduced acuity (8/8) and ocular palsy (13/13) and 81.8% of patients with field deficits (9/11). Age, sex, presence of precipitating factors and timing of surgery did not have an impact on neuro-ophthalmic recovery. CONCLUSION: Pituitary apoplexy should be considered in any patient with abrupt onset of neuro-ophthalmic deficits. Prompt medical and surgical management is lifesaving and can lead to significant improvement in visual and cranial nerve deficits.

Primary orbital intraosseous hemangioma.

PURPOSE: Primary orbital intraosseous hemangioma represents a rare, histopathologically benign, vascular tumor of the bony orbit. Only 41 cases have been documented in the literature to date. The authors present 4 new cases of the disease and review the relevant literature. METHODS: Retrospective, multicenter case note analysis of 4 patients with histopathologically confirmed primary orbital intraosseous hemangioma and a systematic review of the English-language literature. RESULTS: Four new cases of cavernous haemangiomata are presented with varying clinical manifestations, radiologic appearances, and treatments. Literature review (including the present 4 cases) yielded 45 cases in total. Presentation is often in the fourth and fifth decades (42% cases), the frontal bone being most commonly affected, followed by the zygoma, sphenoid, and maxilla. Intracranial extension occurred in 4 cases. Median duration of symptoms before presentation was 12 months (range, 1 month to 15 years) and the most frequent presentation was a painless mass, often on the orbital rim. The radiologic findings are reviewed. Histopathologically, the lesions were cavernous in 80%, capillary in 17%, and mixed in 3%; the capillary subtype seemed to be associated with more aggressive disease. Treatment was mainly by surgical excision and occasionally complicated by significant blood loss; preoperative embolization of lesions may reduce bleeding. CONCLUSIONS: Primary orbital intraosseous hemangioma is a rare vascular tumor that typically presents with a mass effect in the orbits of patients in the fourth and fifth decades of life. Preoperatively, it is important to be cognizant of the possible diagnosis as surgery can be complicated by life-threatening hemorrhage.