Ophthalmological Literature Review 2017 Helen Danesh-Meyer MD, PhD, - PowerPoint PPT Presentation

Ophthalmological Literature Review 2017 Helen Danesh-Meyer MD, PhD, FRANZCO Sir William and Lady Stevenson Professor of Ophthalmoloy University of Auckland New Zealand

Areas to be Covered 1. LHON 2. Optic Neuritis and MS 3. NAION 4. OCT-A

Lebers Hereditary Optic Neuropathy • Key Points: • Higher cellular mtDNA content in peripheral blood cells of unaffected heteroplasmic mutation carriers with respect to the affected persons. • This suggest that increase of cellular mtDNA content may prevent loss of vision despite the presence of a heteroplasmic state of LHON primary mutation. • Strengths and Limitations of Paper: Bianco A, Bisceglia L, Russo Let al. High Mitochondrial DNA Copy Number Is a Protective Factor From Vision Loss in Heteroplasmic Leber’s Hereditary Optic Neuropathy (LHON). Invest Ophthalmol Vis Sci. 2017;58:2193 – 2197.

Lebers Hereditary Optic Neuropathy • Key Points: • Co-morbidities identified – two-fold mortality risk • with a specific increased incidence of atherosclerosis and stroke (RR=2.38X) – association between LHON patients and an increased prevalence of neurologic conditions: • demylinating disorders (RR=12.9X), • dementia (RR=4X), epilepsy (RR=3X), • alcohol-related disorders. • Strengths and Limitations of Paper: Vestergaard N,Rosenberg T, Torp-Pedersen C, et al. Increased Mortality and Comorbidity Associated With Leber’s Hereditary Optic Neuropathy: A Nationwide Cohort Study Invest Oph- thalmol Vis Sci. 2017;58:4586 – 4592.

Lebers Hereditary Optic Neuropathy • Key Points: • Natural history of LHON: prospective observational case study – Identified 6 patients who were unaffected mutation carriers who converted to affected status – An increase in the RNFL thickness preceded conversion as early as 4 to 6 months, peaked at conversion, and decreased until individual plateaus. – This suggests that structural changes precede clinically significant vision loss. Hence, the natural history of LHON is not a subacute process, as previously believed, but progresses more slowly, taking up to 8 months to plateau. • Strengths and Limitations of Paper: Hwang TJ, Karanjia R, Moraes-Filho MN, et al. Natural History of Conversion of Leber’s Hereditary Optic Neuropathy . Ophthalmology 2017;124:843- 850

Optic Neuritis and MS • Key Points: • An observational longitudinal study followed 100 patients with relapsing-remitting MS and 50 controls for 5 years. – Patients with MS had thinning of the average RNFL thickness and the P100 latency of visual evoked potentials. – This suggests that there is progressive axonal loss in the optic nerve which was shown to correlate with increased disability and reduced quality of life. • Strengths and Limitations of Paper: Garcia-Martin E, Ara JR, Martin J. Retinal and Optic Nerve Degeneration in Patients with Multiple Sclerosis Followed up for 5 Years. Ophthalmology 2017;124:688-696

Optic Neuritis and MS • Key Points: • Retrospective cross-sectional study considered the diagnostic error rate of optic neuritis. – An overdiagnosis rate of nearly 60% was shown for those referred with acute optic neuritis. – Overdiagnosis was most commonly caused b: • y errors in taking the history in particular related to eye pain. • Discounting normal examination (iImportantly, a RAPD was one of the more consistent examination findings that correlated with a true diagnosis of optic neuritis and its absence should lead to consideration of other diagnosis. • Misinterpreting MRI findings also led to diagnostic errors. In particular, making the diagnosis of opti neuritis in the presence of normal imaging should be cautioned. • Strengths and Limitations of Paper: Stunkel L, Kung NH, Wilson, MA, McClelland CM, Van Stavern, GP. Incidence and Causes of Overdiagnosis of Optic Neuritis. JAMAOphthalmology 2017 Dec 7. doi: 10.1001/jamaophthalmol.2017.5470.

Optic Neuritis and MS • Key Points: • Corneal nerve fiber density in patients with MS. – Corneal confocal microscopy demonstrated significant reduction in corneal nerve fiber density, branch density and length that correlated with a clinical measure of MS severity. – Findings were independent of age, MS duration and stage, and RNFL loss. – Axonal loss occurring in MS is partially independent of primary demyelination, and is predictive of irreversible neurological disability. – This raises the intriguing possibility tht corneal subbasal innervation may be a useful biomarker for the detection of neuroaxonal injury. • Strengths and Limitations of Paper: Petropoulos IP, Kamran S, Li Y, et al. Corneal Confocal Microscopy: An Imaging Endpoint for Axonal Degeneration in Multiple Sclerosis .Invest Ophthalmol Vis Sci. 2017;58:3677 – 3681.

NAION • Key Points: • Association of catarct surgery and NAION • Retrospective study over 5 years • While 9.6% had undergone surgery during the year prior to developing NAION, there was no significant temporal relationship between cataract surgery and the subsequent development of NAION using modern (phacoemulsification) techniques. • Strengths and Limitations of Paper: Moradi A, Kanagalingam S, Diener-West, M, Miller NR. Post – Cataract Surgery Optic Neuropathy: Prevalence, Incidence, Temporal Relationship, and Fellow Eye Involvement Am J Ophthalmol 2017;175:183 – 193.

NAION • Key Points: • A case-control study of 92 patients demonstrated that patients with diabetes who have an NAION event do not have a worse visual outcome. • In nondiabetics the most prevalent risk factor was hyperlipidema (63%), while for diabetics it was both hypertension(83%) and hyperlipidemia (83%). • Diabetes was not correlated with visual outcome, however, ischemic heart disease and older age, independently correlated with worse VA. • Strengths and Limitations of Paper: Sharma S, Kwan S, Fallano KA, Wang J, Miller NR, Subramanian PS. Comparison of Visual Outcomes of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients with and without Diabetes Mellitus. Ophthalmology 2017;124:450-455.

NAION • Key Points: • A prospective study of 10 patients with acute NAION: – aqueous humor samples were shown to have increased levels of vascular endothelial growth factor (VEGF) and lower levels of interleukin-2 – This may have potential implications for therapeutic interventions and is an area worthy of further investigation. • Strengths and Limitations of Paper: Micieli JA, Lam C, Najem K, Margolin EA. Aqueous Humor Cytokines in Patients With Acute Nonarteritic Anterior Ischemic Optic Neuropathy. Am J Ophthalmol 2017;177:175 – 181.

Optical Coherence Tomography Angiography • Key Points: • Case-control studyof 67 patients peripapillary retinal nerve fibre layer(NFL) thickness, macular ganglion cell complex (GCC) thickness and were optic nerve head perfusion were measured. • Compared to patients without MS, patients with MS had both thinner GCC thicknes and decreased optic nerve head perfusion . • Eyes without documented optic neuritis also demonstrated structural loss and decreased optic nerve head perfusion. • Strengths and Limitations of Paper: Spain RI, Liu L, Zhang X, et al.Optical coherence tomography angiography enhances the detection of optic nerve damage in multiple sclerosis. Br J Ophthalmol Published Online First: 16 August 2017. doi: 10.1136/bjophthalmol-2017-310477 .

Optical Coherence Tomography Angiography • Key Points: – Neurological explored with OCTA technology. – A case control study of patients with Alzheimers dementia showed a decrease in retinal vascular density and enlaraged foveal avascular zone. – Significant correlations were found between the the Mini Mental Status Examination and all vascular density parameters. Given the close association between retinal and cerebral circulations deficits. – This raises the interesting question whether microvasculature deficits detected early with OCTA can be used as a new biomarker in the early detection of Alzheimers type dementia or monitoring of its progression and response to therapies. • Strengths and Limitations of Paper: Bulut M, Kurtuluş F, Gözkaya O, et al. Evaluation of optical coherence tomography angiographic findings in Alzheimer’s type dementia. Br J Ophthalmol Published Online First: 09 June 2017. doi: 10.1136/bjophthalmol-2017-310476

Optical Coherence Tomography Angiography • Key Points: • Case-control studyof 67 patients peripapillary retinal nerve fibre layer(NFL) thickness, macular ganglion cell complex (GCC) thickness and were optic nerve head perfusion were measured. • Compared to patients without MS, patients with MS had both thinner GCC thicknes and decreased optic nerve head perfusion . • Eyes without documented optic neuritis also demonstrated structural loss and decreased optic nerve head perfusion. • Strengths and Limitations of Paper: Spain RI, Liu L, Zhang X, et al.Optical coherence tomography angiography enhances the detection of optic nerve damage in multiple sclerosis. Br J Ophthalmol Published Online First: 16 August 2017. doi: 10.1136/bjophthalmol-2017-310477 .