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To report the clinical features of a patient with melanoma-associated retinopathy (MAR) with anti-transient receptor potential cation channel, subfamily M, member 1 (TRPM1) autoantibodies showing concomitant Off-bipolar cell dysfunction.We evaluated a patient with a past history of scalp melanoma presented with sudden-onset shimmering photopsia in both eyes. MAR was confirmed with complete ophthalmic examinations, electronegative electroretinogram (ERG), and the presence of anti-TRPM1 autoantibodies by Western blot analysis. S-cone ERG and photopic On-Off ERG were studied in this patient as well.The patient's best-corrected visual acuity was 6/30 in the right eye and 6/8.6 in the left eye. Fundus and OCT findings were unremarkable. Visual field test showed severe constriction in both eyes. His full-field ERG was electronegative. S-cone ERG recorded preservation of L/M-cone-mediated response and undetectable S-cone-mediated response. Photopic On-Off ERG disclosed attenuated On- and Off-response. Western blot analysis confirmed immunoreactivity of the patient's serum to a 30 kDa TRPM1 recombinant protein. Whole-body positron emission tomography scan detected lymph node metastases in the neck.Anti-TRPM1 autoantibody-positive MAR varies greatly in its presentation and clinical course. We present a case of anti-TRPM1 autoantibody-positive MAR with atypical feature of Off-bipolar cell involvement. A complete electroretinographic study together with identification of the pathogenic antiretinal autoantibodies may help better understand and subclassify the disease in the future.

Introduction: Lenadogene nolparvovec is a promising novel gene therapy for patients with Leber hereditary optic neuropathy (LHON) carrying the m.11778G>A ND4 mutation (MT-ND4). A previous pooled analysis of phase3 studies showed an improvement in visual acuity of patients injected with lenadogene nolparvovec compared to natural history. Here, we report updated results by incorporating data from the latest phase3 trial REFLECT in the pool, increasing the number of treated patients from 76 to 174. Methods: The visual acuity of 174 MT-ND4-carrying patients with LHON injected in one or both eyes with lenadogene nolparvovec from four pooled phase3 studies (REVERSE, RESCUE and their long-term extension trial RESTORE; and REFLECT trial) was compared to the spontaneous evolution of an external control group of 208 matched patients from 11 natural history studies. Results: Treated patients showed a clinically relevant and sustained improvement in their visual acuity when compared to natural history. Mean improvement versus natural history was - 0.30 logMAR (+ 15 ETDRS letters equivalent) at last observation (P

Leber’s hereditary optic neuropathy (LHON) is a maternally transmitted disease caused by mitochondria DNA (mtDNA) mutation. It is characterized by acute and subacute visual loss predominantly affecting young men. The mtDNA mutation is transmitted to all maternal lineages. However, only approximately 50% of men and 10% of women harboring a pathogenic mtDNA mutation develop optic neuropathy, reflecting both the incomplete penetrance and its unexplained male prevalence, where over 80% of patients are male. Nuclear modifier genes have been presumed to affect the penetrance of LHON. With conventional genetic methods, prior studies have failed to solve the underlying pathogenesis. Whole exome sequencing (WES) is a new molecular technique for sequencing the protein-coding region of all genes in a whole genome. We performed WES from five families with 17 members. These samples were divided into the proband group (probands with acute onset of LHON, n = 7) and control group (carriers including mother and relative carriers with mtDNSA 11778 mutation, without clinical manifestation of LHON, n = 10). Through whole exome analysis, we found that many mitochondria related (MT-related) nuclear genes have high percentage of variants in either the proband group or control group. The MT genes with a difference over 0.3 of mutation percentage between the proband and control groups include AK4, NSUN4, RDH13, COQ3, and FAHD1. In addition, the pathway analysis revealed that these genes were associated with cofactor metabolism pathways. Family-based analysis showed that several candidate MT genes including METAP1D (c.41G > T), ACACB (c.1029del), ME3 (c.972G > C), NIPSNAP3B (c.280G > C, c.476C > G), and NSUN4 (c.4A > G) were involved in the penetrance of LHON. A GWAS (genome wide association study) was performed, which found that ADGRG5 (Chr16:575620A:G), POLE4 (Chr2:7495872T:G), ERMAP (Chr1:4283044A:G), PIGR (Chr1:2069357C:T;2069358G:A), CDC42BPB (Chr14:102949A:G), PROK1 (Chr1:1104562A:G), BCAN (Chr 1:1566582C:T), and NES (Chr1:1566698A:G,1566705T:C, 1566707T:C) may be involved. The incomplete penetrance and male prevalence are still the major unexplained issues in LHON. Through whole exome analysis, we found several MT genes with a high percentage of variants were involved in a family-based analysis. Pathway analysis suggested a difference in the mutation burden of MT genes underlining the biosynthesis and metabolism pathways. In addition, the GWAS analysis also revealed several candidate nuclear modifier genes. The new technology of WES contributes to provide a highly efficient candidate gene screening function in molecular genetics.

A seven-month-old girl presented with bilateral roving nystagmus, hyperopia, and retinal dystrophy, and was brought to our ophthalmology clinic. Visual-evoked potentials (VEPs) were non-recordable in both the eyes. No other systemic symptoms or abnormalities were observed. Whole exome sequencing (WES) identified a compound heterozygous mutation in the

The mutations in the genes encoding the subunits of complex I of the mitochondrial electron transport chain are the most common cause of Leber’s hereditary optic neuropathy (LHON), a maternal hereditary disease characterized by retinal ganglion cell (RGC) degeneration. The characteristics of incomplete penetrance indicate that nuclear genetic and environmental factors also determine phenotypic expression of LHON. Therefore, further understanding of the role of mutant mitochondrial nicotinamide adenine dinucleotide dehydrogenase subunit proteins and nuclear genetic factors/environmental effects in the etiology of LHON is needed. In this study, we generated human-induced pluripotent stem cells (hiPSCs) from healthy control, unaffected LHON mutation carrier, and affected LHON patient. hiPSC-derived RGCs were used to study the differences between affected and unaffected carriers of mitochondrial DNA point mutation m.11778G > A in the MT-ND4 gene. We found that both mutated cell lines were characterized by increase in reactive oxygen species production, however, only affected cell line had increased levels of apoptotic cells. We found a significant increase in retrograde mitochondria and a decrease in stationary mitochondria in the affected RGC axons. In addition, the messenger RNA and protein levels of KIF5A in the LHON-affected RGCs were significantly reduced. Antioxidant N-acetyl-L-cysteine could restore the expression of KIF5A and the normal pattern of mitochondrial movement in the affected RGCs. To conclude, we found essential differences in the mutually dependent processes of oxidative stress, mitochondrial transport and apoptosis between two LHON-specific mutation carrier RGC cell lines, asymptomatic carrier and disease-affected, and identified KIF5A as a central modulator of these differences.

To assess the long-term refractive status, visual outcome, astigmatism, and the change in biometric optic components in older adolescents up to age 17 years with threshold retinopathy of prematurity (ROP) treated with diode laser.A retrospective, longitudinal study in which cycloplegic refraction, keratometry, and the biometric measurement of optic components were performed on 28 consecutive preterm eyes with laser-treated threshold ROP at age 17 years. The study results were statistically analysed and compared with age-matched full-term control.All patients with ROP had myopia (average spherical equivalent of - 6.35 D, ranges from - 1.25 to - 12.38 D), and 12 eyes (43%) were highly myopic (spherical equivalent - 6.0 D). Threshold ROP eyes exhibited a significantly poorer visual acuity (P 0.001), greater cylinder refractive error (P 0.001), higher corneal astigmatism (P 0.001), and flatter horizontal corneal curvature (P = 0.01) compared with age-matched controls. Biometric optic components analysis revealed a significant shallower anterior chamber depth (P 0.001), thicker lens (P 0.001), and shorter axial length (P = 0.021) in laser-treated ROP eyes compared with age-matched controls.In this 17-year longitudinal study, a higher prevalence of myopia and astigmatism was observed in laser-treated threshold ROP eyes compared with age-matched control eyes. Myopia and astigmatism in laser-treated ROP eyes typically progress through adolescence after school age. Therefore, we recommend that preterm patients with laser-treated threshold ROP should attend regular follow-up not only for refractive status but also for structural change of anterior segment until their adolescence.

There is no consensus regarding the classification of optic neuritis, and precise diagnostic criteria are not available. This reality means that the diagnosis of disorders that have optic neuritis as the first manifestation can be challenging. Accurate diagnosis of optic neuritis at presentation can facilitate the timely treatment of individuals with multiple sclerosis, neuromyelitis optica spectrum disorder, or myelin oligodendrocyte glycoprotein antibody-associated disease. Epidemiological data show that, cumulatively, optic neuritis is most frequently caused by many conditions other than multiple sclerosis. Worldwide, the cause and management of optic neuritis varies with geographical location, treatment availability, and ethnic background. We have developed diagnostic criteria for optic neuritis and a classification of optic neuritis subgroups. Our diagnostic criteria are based on clinical features that permit a diagnosis of possible optic neuritis; further paraclinical tests, utilising brain, orbital, and retinal imaging, together with antibody and other protein biomarker data, can lead to a diagnosis of definite optic neuritis. Paraclinical tests can also be applied retrospectively on stored samples and historical brain or retinal scans, which will be useful for future validation studies. Our criteria have the potential to reduce the risk of misdiagnosis, provide information on optic neuritis disease course that can guide future treatment trial design, and enable physicians to judge the likelihood of a need for long-term pharmacological management, which might differ according to optic neuritis subgroups.

ObjectiveREFLECT is the first randomised, double-masked, placebo-controlled multicentre phase 3 clinical trial that evaluated the efficacy and safety of bilateral intravitreal (IVT) injection of lenadogene nolparvovec in subjects with Leber hereditary optic neuropathy carrying the m.11778G>A mutation.Methods and analysisA total of 98 subjects were enrolled with vision loss of ≤12 months. The subjects were randomised to one of two treatment arms with all subjects receiving an intravitreal (IVT) injection of lenadogene nolparvovec in their first affected eye and the second-affected eye randomised to receive IVT of either lenadogene nolparvovec or placebo.ResultsThe majority of subjects were male with a mean duration of vision loss of 8.3 months. All but one subject experienced bilateral loss of vision at the time of injection. The mean best-corrected visual acuity of first-affected eyes was worse compared with second/not-yet-affected eyes. Analysis of retinal anatomical parameters showed increased thinning in the first-affected eyes when compared with the second/not-yet-affected eyes with both treatment arms showing significant changes compared with unaffected individuals.ConclusionThe REFLECT trial is the third and the largest phase 3 clinical study evaluating lenadogene nolparvovec in m.11778G>A Leber hereditary optic neuropathy (LHON) subjects. The observed demographics in REFLECT are consistent with previous reports in LHON subjects in the acute and dynamic phases of LHON disease. Combined with the visual function and anatomical parameters obtained in the previous RESCUE and REVERSE trials, REFLECT has provided a uniformly collected data set that should help direct future LHON clinical trials.

Leber’s hereditary optic neuropathy (LHON) is the maternally inherited mitochondrial disease caused by homoplasmic mutations in the mitochondrial electron transport chain. The pathological mechanism of LHON is still unclear. The feature of incomplete penetrance indicates that complex factors are involved in the phenotypic expression of LHON. Therefore, the application of appropriate experimental models in the etiology of LHON requires further understanding. The traditional cell models of LHON were non-neuronal cells carrying mtDNA mutation, such as patient fibroblasts and cybrid cells, however, mutation is necessary but not sufficient to cause LHON. Ideal models of LHON should be capable of presenting incomplete penetrance that distinguishes healthy carrier cells from affected cells. In this chapter, we review the pathophysiology of LHON as it relates to old, new, and future models. We further compare the advantages and disadvantages of different models of LHON and clarify unanswered questions that might help to explore the new model in the future.

Background Glutaric aciduria type 1 (GA-1) is an organic acidemia with potentially severe neurological sequelae. In Taiwan, newborn screening (NBS) for GA-1 began in 2001, but large-scale reporting is lacking. This study describes Taiwan's largest newborn screening population to date. Methods Between 2001 and 2015, 1,490,636 newborns were screened for GA-1. Confirmatory examinations included the carnitine loading test. Confirmed patients were treated with a low lysine diet, carnitine, and high-energy intake during illness. Clinical, laboratory, and neuroimaging data were analyzed. Results Fourteen newborns were diagnosed with GA-1 (incidence: 1/106,474). C5DC concentration was clearly increased after carnitine loading in the affected newborns, but not in false-positive newborns (p = 0.004), indicating that this test is useful as an adjuvant diagnostic method. Eleven patients followed in our hospital were enrolled, namely nine NBS patients and two patients diagnosed clinically. IVS10-2A>C was the most common mutation. Two novel mutations (T36fs and N291K) were identified. Pendular nystagmus was found in two pediatric GA-1 patients. The corresponding pathology was optic atrophy in one patient, but remained undetermined in the other patient. The frequency of encephalopathic crisis decreased substantially following NBS. Among patients diagnosed by NBS, cognitive functioning was better among patients with good compliance than patients with poor compliance (p = 0.03). Abnormalities were detected by brain MRI including diffusion-weighted imaging and apparent diffusion coefficient maps; these affected various brain regions at different stages of the disease. Basal ganglion injuries occurred after an encephalopathic crisis. White matter disease was prevalent among older patients, either with or without an encephalopathic crisis. Conclusion Early diagnosis by newborn screening followed by full compliance with treatment guidelines is important to a good outcome.

The aim of the study was to evaluate the influence of carotid angioplasty and stenting (CAS) on retinal microvasculature using optical coherence tomography angiography (OCTA) in patients with severe carotid stenosis. 20 patients with severe carotid stenosis underwent comprehensive ophthalmic examinations and OCTA before and one month after CAS. Automated algorithms were used to quantify vessel density in the macular superficial vascular complex (SVC), deep vascular complex (DVC), and radial peripapillary capillary (RPC) around the optic disc. Eyes on the operated side constituted the ipsilateral eye group, and the other eye constituted the fellow eye group. In the ipsilateral eye group, the vessel density in the DVC increased significantly after stent implantation (P = 0.010), but the vessel density change in the SVC was not statistically different (P = 0.999). In the fellow eye group, the vessel density in the SVC (P = 0.028) and DVC (P = 0.034) were significantly increased after stent implantation. The vessel density in the RPC did not significantly change in the ipsilateral (P = 0.363) or fellow (P = 0.878) eye groups. This study shows that unilateral CAS for severe carotid stenosis increases macular vessel densities in both eyes.

Purpose To investigate whether daily changes in ambient air pollution were associated with an increased risk of central retinal artery occlusion (CRAO). Design Retrospective population-based cohort study. Participants We identified patients newly diagnosed with CRAO between 2001 and 2013 in a representative database of 1 000 000 patients that were randomly selected from all registered beneficiaries of the National Health Insurance program in Taiwan. We identified air pollutant monitoring stations located near these patients' residences in different administrative areas in Taiwan to determine the recorded concentrations of particulate matter ≤2.5 μm (PM 2.5 ), particulate matter ≤10 μm (PM 10 ), nitrogen dioxide (NO 2 ), sulfur dioxide (SO 2 ), and ozone (O 3 ). Patients without corresponding monitoring stations were excluded. Methods We used a time-stratified case-crossover study design and conditional logistic regression analysis to assess associations between the risk of CRAO and the air pollutant levels in the days preceding each event. Main Outcome Measures Odds ratios (ORs) and 95% confidence intervals (CIs). Results We enrolled 96 patients with CRAO in this study. The mean age was 65.6 years (standard deviation, 12.7 years) and 67.7% of patients were male. The risk of CRAO onset was significantly increased (OR, 1.09; 95% CI, 1.01–1.17; P = 0.03) during a 5-day period following a 1 part per billion increase in NO 2 levels. After multipollutant adjustment, the increase in risk was most prominent after 4 days (OR, 1.40; 95% CI, 1.05–1.87; P = 0.02) to 5 days (OR, 2.16; 95% CI, 1.10–4.23; P = 0.03) of elevated NO 2 levels in diabetic patients. The risk of CRAO onset also significantly increased in patients with hypertension and in patients ≥65 years old, after 1 day of elevated SO 2 levels (OR, 1.88; 95% CI, 1.07–3.29; P = 0.03 and OR, 1.90; 95% CI, 1.13–3.21; P = 0.02, respectively). The transient concentration of the other air pollutants, including PM 2.5 , PM 10 , and O 3 , did not significantly affect the occurrence of CRAO in this study. Conclusions These results demonstrated a positive association between air pollution and CRAO onset, particularly in patients with diabetes or hypertension and those older than 65 years.

Background Most cavernous sinus dural arteriovenous fistulas (CSDAVFs) present with benign neuro-ophthalmic symptoms. CSDAVFs manifesting with aggressive neurologic symptoms are rare. The purpose of this study was to analyze the different angioarchitectures of aggressive CSDAVFs and to report our experiences of embolization. Methods Over the past 10 years, a total of 118 CSDAVFs were managed by embolization. From the databases containing such patient information, nine patients (7.6%) were found to have aggressive CSDAVFs presenting with neurologic deficits. There were seven women and two men, ranging in age from 51 years to 78 years (mean, 66 years). We retrospectively analyzed the angioarchitectures of aggressive CSDAVFs, further reviewing patient and angiographic as well clinical outcomes after embolization. Results The cause of clinically aggressive CSDAVFs was insufficient fistula drainage because of occlusion ( n = 6) or stenosis ( n = 1) of the inferior petrous sinus (IPS) or compartment of IPS–cavernous sinus ( n = 2) with fistula flow reflux to the veins of brainstem ( n = 7) leading to brainstem ischemia, while two fistula flow reflux to the cortical vein leading to cerebral infarction. Transvenous embolization via IPS to fistula was achieved in one case; six patients underwent transorbital access, while transarterial embolization was performed in two cases. Total fistula occlusion was achieved in eight CSDAVFs. All patients had total ( n = 7) or partial ( n = 2) resolution of their symptoms gradually within 6 months. One patient undergoing transarterial embolization had limb weakness because of inadvertent pial artery occlusion. Their overall mean clinical follow-up period was 17 months. Conclusion Aggressive CSDAVFs are associated with occlusion/stenosis of the IPS or compartment of IPS–cavernous sinus with leptomeningeal reflux. In this limited case series, aggressive CSDAVFs most presented with brainstem ischemia, followed by nonhemorrhagic/hemorrhagic stroke in the cerebrum. Embolization through various access routes is a feasible method to manage these aggressive CSDAVFs, with an acceptable level of periprocedural risks.

A 57-year-old male had hyperthyroidism for 3 years. He first suffered diplopia with right eye fullness 9 months ago. He received methylprednisolone pulse therapy for 3 days at a local hospital under the impression of thyroid eye disease with right optic nerve compression. The vision in his right eye improved after treatment. Six months later, he began to suffer from left eye fullness and blurred vision OS. Left visual acuity dropped to 6/60 then. He received methylprednisolone pulse therapy for 3 days, and his vision improved to 6/20 OS. He was then discharged with oral prednisolone tapered completely within 2 weeks. He came to our clinic 2 months later due to persistent diplopia and blurred vision in the left eye. Ophthalmologic examination showed visual acuity of 6/7.5 OD and 6/30 OS. He could identify 15 plates in the right eye and 10 plates in the left eye using the Ishihara test. Intraocular pressures were normal. Bilateral eyelids were mildly swollen. A prism cover test showed that there were 4 prism diopters of esotropia on primary gaze, which increased to 8 prism diopters on left gaze. Mild cortical opacity was found in both lenses. Fundoscopic examination showed disc swelling in the left eye. In addition, horizontal retino-choroidal foldings were identified in the left macula (Fig. 28.1). OCT demonstrated an increased peripapillary retinal nerve fiber layer (RNFL) thickness of 283 μm in the left eye, with decreased ganglion cell-inner plexiform layer (GC-IPL) thickness over macular region (Fig. 28.2). Fluorescein angiography revealed dye staining on the left disc and retino-choroidal foldings over the macula (Fig. 28.3). A visual field examination showed a constricted visual field in the left eye (Fig. 28.4). An orbital CT scan revealed enlargement of the bilateral superior rectus, medial rectus, and inferior rectus, with left optic nerve compression (Fig. 28.5). One week later, his vision decreased to 6/60 in the left eye, and color sense worsened to nine plates. MR imaging showed similar findings of extraocular muscle enlargement, with compression of the left optic nerve (Fig. 28.6). Surgical decompression and pulse therapy were explained to the patient, and the patient elected steroid pulse therapy first. He received methylprednisolone pulse therapy, and his visual acuity improved to 6/15 OS on the third day of steroid treatment. His vision improved to 6/6.7 OD and 6/8.6 OS 1 month later, and his left peripapillary RNFL thickness decreased to 138 μm.

A 51-year-old female was referred to our department by a local practitioner with the complaint of blurry vision in the left eye for 2 months. She had been diagnosed with type 1 neurofibromatosis, presenting with multiple neurofibromas over her neck and trunk (Fig. 45.1). Her corrected vision was 6/6 in the right eye and 6/60 in the left eye. Intraocular pressures were normal. She could identify 12 plates in the right eye and 0 plate in the left eye with the Ishihara test. Anterior segments were normal, except for RAPD in the left eye. Fundoscopic examination showed disc pallor in the left eye (Fig. 45.2). A visual field examination revealed mild constriction in the right eye and near total obscuration in the left eye (Fig. 45.3). MRI showed a 32 mm lesion in the frontal base, planum sphenoidale, and tuberculum sella with isointense signals on T1-weighted and T2-weighted images. The lesion was homogeneously enhanced with gadolinium. In addition, a dural tail sign was noted on a sagittal view MR scan (Fig. 45.4). The patient underwent a craniotomy, and the pathologic report came back as a transitional type of meningioma.

A 64-year-old male reported suffering from blurred vision OS for 2 years. He has a past medical history of asthma under steroidal control. He received cataract surgery in both eyes about 10 years ago. The patient also reported eye discomfort with associated heat sensations in the left eye recently. He visited a local ophthalmologist who referred him to us under the impression of left optic neuropathy. Best-corrected visual acuity was 6/6 in the right eye and 6/12 in the left. He could identify 15 plates in the right and 14 plates in the left using the Ishihara test. Slit lamp examination showed a clear cornea with guttata OU and pseudophakia in both eyes. Fundoscopic examination revealed optic disc pallor in the left eye (Fig. 26.1). OCT showed mild thinning of the peripapillary retinal nerve fiber layer (RNFL) in the left eye with moderate loss of the ganglion cell-inner plexiform layer (GC-IPL) in the macula OS (Fig. 26.2). No vascular anomaly could be found on fluorescein angiography. A visual field examination showed a cecocentral scotoma in the left eye (Fig. 26.3). An MRI of the orbit revealed inflammation over the left orbital region with mild enhancement (Fig. 26.4). He was admitted for steroid pulse therapy for 3 days and tapered gradually thereafter. One week later, his vision recovered to 6/7.5 in the left eye and remained stable over the following 2 years with low-dose oral steroids.

A 70-year-old female presented with complaints of gradual blurring OU for 2 months. Her vision dropped from 6/6 to 6/20 in the right eye and from 6/12 to 6/60 in the left within 2 months. According to her family, her medical history included hypertension, cardiac arrhythmia, and controlled hypothyroidism under Eltroxin. She was diagnosed with pulmonary tuberculosis 11 months prior and has since been taking AkuriT-3 (Rifampin 150 mg), isoniazid (75 mg), and ethambutol (275 mg) 4# QD. These medications were discontinued 9 months ago and changed to PZA (500 mg) 3# QD. PZA was used for half a year and was changed to Rifinah (300 mg) 2#QD for 3 weeks and again changed to Levofloxacin (500 mg) 1# QD and Rifampin (150 mg) 4# QD. Her vision notably worsened in the most recent 2 months, despite active revision of antituberculosis medications, so she was referred to our department.

A 5-year-old girl visited our clinic with her mother. Her mother reported that her daughter usually looked at objects with a lateral gaze. She also often runs into things with her right side and easily gets the right side of her clothes dirty while eating. The patient presented with multiple erythematous patches on her right forehead (Fig. 19.1) and was previously diagnosed to have Sturge-Weber syndrome. She also had a past medical history of epilepsy under medical control. Her visual acuity was 6/6 in both eyes. Intraocular pressures were normal. She exhibited orthophoria with a full range of movement in both eyes. Fundoscopic examination showed large cupping of the optic discs in both eyes (Fig. 19.2). OCT examination revealed decreased thickness of the peripapillary retinal nerve fiber layer (RNFL) in both eyes. In addition, it demonstrated a special pattern of hemi-loss of the left-sided ganglion cell-inner plexiform layer (GC-IPL) (Fig. 19.3). A visual field examination showed incongruous right homonymous hemianopia in both eyes (Fig. 19.4), corresponding with the hemi-loss of left GC-IPL observed. We arranged a CT scan of the brain which showed several spots of high density in the left parietal region (Fig. 19.5). A vascular lesion or migration disorder was suspected. MR imaging of the brain revealed smaller-sized left temporo-parieto-occipital lobes, associated with less gyration, extensive pia enhancement, and relatively larger left-sided choroid plexuses. MR angiography showed extensive leptomeningeal angiomatosis over left side (Fig. 19.6). These imaging findings are compatible with the CNS involvement present in Sturge-Weber syndrome.

A 37-year-old male reported suffering with blurred vision OU for a long time. He was diagnosed with multiple sclerosis at a local hospital approximately 4 years ago. He had received methylprednisolone treatment, but dizziness persisted. He then visited our Neurology department complaining of dizziness and loss of balance for 8 months. He also cited experiencing blurry vision, motion and speech slowness, poor appetite, and hand tremors. Ophthalmic consultation reported a visual acuity of 6/20 in the right eye and 6/15 in the left. Moderate limitation of adduction was noted in both eyes (Fig. 34.1). Both eyes showed dissociated abducting nystagmus (Video 34.1). Slit lamp and fundoscopic examinations were normal. The visual field was full in both eyes. MR imaging of the brain showed multiple abnormal high signals on T2WI involving bilateral deep white matter, corpus callosum, occipital periventricular regions, and periaqueductal regions of the pons and medulla (Fig. 34.2). The patient also underwent a lumbar puncture with opening and closing pressures of 108 and 57 mmH2O, respectively. IgG index was 2.7. He also received thiamine treatment, but this treatment was not effective per the patient. He was discharged under the impression of multiple sclerosis.

A 38-year-old male presented with complaints of persistent blurring of his right eye since ocular trauma that occurred 1 month ago. He had an ocular injury OD hit by an iron rod during fighting. He underwent primary repair of his conjunctival laceration OD at another hospital. However, blurred vision persisted in the right eye postoperatively without any notable improvement. He visited our hospital for concerns about visual impairment.

A 56-year-old male presented with complaints of gradual blurring in his left eye for 2 months. He was diagnosed with anterior ischemic optic neuropathy and referred to our department. The referring note cited a lower altitudinal defect in the left eye as of 3 weeks ago. The patient did not have a medical history of diabetes or hypertension, but did suffer from cardiac arrhythmias which were controlled under regular amiodarone treatment. No history of alcohol drinking or cigarette smoking was noted. Ophthalmoscopic examination showed a visual acuity of 6/6 in the right eye and 6/10 in the left. He could identify 15 plates in the right eye and only 4 plates in the left eye with the Ishihara test. Intraocular pressure was normal. Corneal verticillata was noted in both eyes. The anterior chambers were quiet and the lens was clear OU. A mild relative afferent pupillary defect was found in the left eye. Pale swelling of the left optic disc was found in the left fundus (Fig. 12.1). Fluorescein angiography revealed hypoperfusion of the upper disc OS in early phase and dye staining on left disc at late phase (Fig. 12.2), which is compatible with anterior ischemic optic neuropathy. A visual field test showed a constricted field associating with inferior cecocentral scotoma in the left eye (Fig. 12.3). Supportive treatment was given under the impression of anterior ischemic optic neuropathy. His vision deteriorated to 6/12 in the left eye with persistent disc edema 2 weeks later. Since the disc edema persisted for more than 3 months after onset, amiodarone was discontinued under his medical doctor’s supervision under the impression of suspected amiodarone-associated optic neuropathy. Six weeks later, his left vision recovered to 6/8.6 with marked resolution of disc edema (Fig. 12.4). His visual acuity recovered to 6/6 in the left eye 1 year later. His visual field improved partially after long-term follow-up (Fig. 12.5).

A 15-year-old girl presented with complaints of blurred vision, nystagmus, and diplopia for 1 week. She had been diagnosed with anorexia nervosa 3 years ago based on parameters of weight and her reluctance to food intake. In the most recent 6 months, she collapsed multiple times from poor nutrition, was in a constantly depressed mood, and had also developed amenorrhea. In the past 1 week, she complained of blurring, diplopia, and nystagmus. Ecchymosis was found over her right cheek region. Gingival bleeding was noted as well. Her best-corrected vision was 6/60 (−6.25–0.75 × 11) in the right eye and 6/60 (−6.25–0.75 × 176) in the left eye. A Hirschberg test was orthophoric. Extraocular movement was full and free (Fig. 35.1). Upbeat nystagmus could be found on primary gaze, which increased on upgaze and decreased on lateral gazes and turned into downbeat on downgaze (Video 35.1). Anterior segments were normal. Preretinal and flame-shaped retinal hemorrhage was found over the superotemporal and inferotemporal arcades in both eyes (Fig. 35.2). Mildly increased thickness of the peripapillary retinal nerve fiber layer (RNFL) was found in the left eye. A fluorescein angiography demonstrated blocked fluorescein over retinal hemorrhages and dye staining on bilateral optic discs (Fig. 35.2). Relative central scotoma was found in both eyes (Fig. 35.3). The patient was admitted under the impression of Wernicke’s encephalopathy with upbeat nystagmus and nutritional optic neuropathy.

A 14-year-old boy went hiking on a mountain with an altitude of 3275 m. He felt periorbital discomfort and intermittent mosaic vision in both eyes. A sudden loss of vision in the left eye was noticed 3 days later. He visited a local hospital 1 week later. His best-corrected visual acuity was 6/6 in the right eye and hand motion at 20 cm in the left. He was unable to identify any plates with left eye using the Ishihara test, whereas the test was normal in the right eye. There was reported pain on eye movement. Faint epithelial opacity could be found in both corneas (Fig. 56.1). A relative afferent pupillary defect was found on the left side. A pale and swollen optic disc was found in the left eye (Fig. 56.2). Fluorescein angiography showed severely delayed filling of the left disc (Fig. 56.3). The visual field was near totally obscured in the left eye, and the visual evoked potential was poor on the left side. A peripheral blood examination including blood cell count, autoimmune profile, infectious agent, ESR, and CRP was negative. CT scan showed an enlarged left optic nerve with contrast enhancement (Fig. 56.4).

A 59-year-old woman presented with sudden-onset eyelid swelling, ptosis, diplopia, mild pulsation, and mild pain of the right periorbital area for 4 days. She had gone to a local hospital and received antihistamine treatment. She was referred to our hospital for further investigation. The patient had no known history of systemic diseases except for hyperlipidemia. She also denied previous trauma and allergies. Her vision was 6/6 in both eyes. Mild lid ptosis was noted in the right side. A Krimsky test revealed a 35-prism diopter of exotropia in the right eye. In addition, extraocular movement showed severe limitations in adduction, supraduction, and infraduction of the right eye (Fig. 27.1). Anterior segments and fundoscopic examination were normal. Pupils were symmetric and reactive to light. An MR imaging study showed an enhancing lesion over the right cavernous sinus (Fig. 27.2) and segmental stenosis of the right internal carotid artery (ICA). The patient was admitted for lumbar puncture which showed an opening and closing pressure of 78/55 mmH2O, respectively. CSF analysis showed no white blood cells and a normal protein level and IgG index (0.64). Pulse therapy with methylprednisolone was given. Her orbital pain was relieved after steroid treatment and eye movement improved gradually. Her eye position returned to orthophoric with a full range of motion observed 1 month later (Fig. 27.3).

A 57-year-old male presented with complaints of blurred vision OU for 1 week. He had received coronary artery bypass surgery 3 months ago and did not have any postoperative complications. His best-corrected visual acuity was 6/10 in both eyes. Intraocular pressures were normal. He could identify six plates in the right eye and seven plates in the left eye using the Ishihara test. Slit lamp examination showed normal anterior segments. Pupils were symmetric and reactive to light. Ophthalmoscopic examination revealed normal fundi in both eyes. Superior visual field defects were noted bilaterally (Fig. 51.1). MRI showed multiple lesions over the bilateral temporo-occipital lobe and left occipital lobe (Fig. 51.2).

An 18-year-old male student came to the clinic because of gradual blurring of his right vision for the past 2 weeks. His vision dropped to 1/60 in the right eye, and he had normal acuity of 6/6 in the left. Color sense was only mildly impaired; he could identify 14 plates in the right eye and 15 plates in the left with the Ishihara test. Ophthalmoscopic examination showed a relatively normal disc in both eyes (Fig. 7.1) and a dense central scotoma in the right field (Fig. 7.2). Visual evoked potential was flat in the right eye and normal in the left eye (Fig. 7.3). However, pattern ERG was normal in both eyes with a relatively normal N95 in the right eye (Fig. 7.4). Increased peripapillary nerve fiber layer (RNFL) thickness was noted in the right eye by OCT examination. The average RNFL thickness was 115 μm in the right eye and 99 μm in the left (Fig. 7.5). Loss of the nasal half of the ganglion cell complex was also found in the right eye. The average GCL-IPL thickness was 71 μm in the right and 90 μm in the left eyes (Fig. 7.5). He received methylprednisolone 250 mg q6h intravenously for 3 days. Nevertheless, his vision did not recover. Peripheral blood DNA analysis revealed a mtDNA 11778G > A mutation. Two months later, the RNFL was still thickened in the right eye with average thickness of 118 μm in the right compared to 102 μm in the left. Nonetheless, the GCC complex was near totally lost in the right eye (Fig. 7.6).

A 14-year-old boy presented with complaints of diplopia for 1 month. He had a minor head injury 1 week before the onset of diplopia. He was hit in the head with a ball, but did not report feeling any significant discomfort at that time. He began to experience double vision afterward and visited a local ophthalmologist. He was subsequently transferred to our clinic. His vision was 6/6.7 in the right and 6/6 in the left. Color vision and intraocular pressures were normal. Anterior segments were normal. Ophthalmoscopic examination showed normal fundi in both eyes (Fig. 40.1). A prism cover test revealed 1 prism diopter of left hypertropia on primary gaze and increased measurements on right gaze and left tilt. The results of a park three-step test were compatible with left trochlear nerve palsy. An extraocular movement examination showed moderate limitation of upgaze in both eyes (Fig. 40.2, Video 40.1). Visual field testing revealed enlarged blind spots in both eyes (Fig. 40.3). MRI showed a pineal tumor with cystic space, which was isointense on T1-weighted images and hyperintense on T2-weighted images. The tumor was enhanced after gadolinium injection (Fig. 40.4). Under the impression of germ cell tumor, there was subtle seeding into third ventricle noted along with associated obstructive hydrocephalus. A peripheral blood examination demonstrated increased AFP (3295 ng/mL) and β-HCG (151 mIU/mL). The patient hesitated to receive surgical biopsy, and there was subsequent loss to follow-up.

A 10-year-old girl presented with complaints of decreased vision in the right eye for 2 weeks. She visited another hospital and was told she had optic neuritis. Steroid pulse therapy was suggested there, and the patient’s parents wished to consult us for a second opinion. She had a nasal allergy but was otherwise healthy. Family history for hereditary disease was negative. Her best-corrected vision was 6/60 in the right eye and 6/6.7 in the left. She could identify only 1 plate in the right eye and 15 plates in the left eye using the Ishihara test. Intraocular pressure was normal. Slit lamp examination showed normal anterior segments. Relative afferent pupillary defect (RAPD) was found in the right eye. Optic disc swelling with scalloping margins was noted in the right fundus (Fig. 9.1). Fluorescein angiography showed early hypoperfusion around the right optic disc, with mild dye staining on the disc at late phase (Fig. 9.2). A visual field examination showed an inferotemporal defect in the right eye (Fig. 9.3). CT scan showed a tubular enlargement of the right optic nerve without calcification (Fig. 9.4). MRI revealed an enlarged right optic nerve with buckle sign; the tumor was isointense on a T1-weighted image and hyperintense on T2-weighted images (Fig. 9.5).There was only weak enhancement over the optic nerve tumor. These imaging findings were compatible with the diagnosis of optic nerve glioma.

An 81-year-old female reported suffering from a severe headache on the night of July 24th, and she visited the internal medicine clinic the next morning. She was found to have bacteriuria with mild fever and started treatment with Augmentin and acetaminophen. She had a past medical history of diabetes mellitus that was controlled. She developed eyestrain, eye discomfort, and micropsia on the morning of July 26th. Everything was reported to look very thin, small, and unreal. For example, the patient described her own hands to have looked like chicken claws, and people around her to have looked distant and paper-thin.

A 47-year-old male reported suffering from headache and diplopia for 10 years that has become worse in the most recent 2 years. He presented to the ophthalmology department because of sudden blurring in the left eye 1 month ago, which resolved spontaneously later. His vision was 6/5 with glass correction in both eyes. Anterior segments were unremarkable. Fundoscopic examination was normal (Fig. 49.1), and OCT revealed normal thickness of the peripapillary retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GC-IPL) over the macula. A visual field examination was normal except for small focal defects over the superior regions. However, an MRI revealed a 2 × 1 × 1.4 cm nodule in the anterior aspect of the left cavernous sinus extending to the left superior orbital fissure (Fig. 49.2). Hemangioma or meningioma in the cavernous sinus was suspected. After consultation, the patient decided to receive r-knife radiosurgery 1 month later. Three days after the radiosurgery, he reported experiencing blurriness in the left eye. Emergent ophthalmic consultation revealed decreased visual acuity of 6/60 with glass correction in the left. He could identify 15 plates in the right eye and 0 plate in the left with the Ishihara color test. Visual field testing revealed a dense central and inferotemporal scotoma in the left eye [Fig. 49.3]. Steroid pulse therapy was given to reduce tissue edema following the radiosurgery. His left vision recovered to 6/5 1 month after steroid treatment. Nonetheless, it progressed to hand motion under oral steroid 2 months later. He decided to undergo a craniotomy for removal of the tumor. The pathological report came back as a schwannoma of the cavernous sinus. His vision recovered to 6/6 with normal visual fields [Fig. 49.4] 6 weeks after the surgery.

A 51-year-old male presented with complaints of diplopia for 1 month. The patient was a hepatitis B carrier. His vision was normal with an acuity of 6/6 in both eyes. A prism cover test showed 8 prism diopters of left hypertropia, which increased to 14 prism diopters on left gaze and decreased to 2 prism diopters on right gaze. The left hypertropia was 4 prism diopters on right head tilt and increased to 10 prism diopters on left tilt. Extraocular movements revealed limited supero-nasal movement in the right eye (Fig. 33.1). Anterior segments were normal with clear lens in both eyes. Fundoscopic examination showed normal posterior poles (Fig. 33.2). A Maddox double rod test found a 3° of intorsion in the right eye. A Worth four-dot test disclosed diplopia on both near and far targets. The patient could identify the fly only in the Titmus stereoacuity test. Antinuclear antibody was found to be 1:160× positive, while immunoglobulins and complements were normal. Tenderness over the right trochlear region was also noticed. MRI showed enhancement over the right superior oblique tendon (Fig. 33.3). Under the impression of right trochlear tendonitis, we gave him an injection of 10 mg triamcinolone acetonide over the right trochlear region. One month later, the patient felt much improved with better vision and relief of pain and diplopia. His range of movement improved in the supero-nasal direction of the right eye (Fig. 33.4).

A 21-year-old female presented at another clinic for concerns about her eyeglass prescription. She was referred to us under the impression of disc edema OS. Her best-corrected visual acuity was 6/6 in both eyes. A prism cover test showed that there was intermittent exotropia of 8 prism diopters. Slit lamp examination was normal. Disc edema with mildly tortuous retinal vessels was noted in the left eye (Fig. 10.1). There is normal vascular perfusion in early phase and mild staining on optic disc in late phase (Fig. 10.1). A slightly enlarged blind spot was noted in the patient’s left visual field (Fig. 10.2). MRI of the optic nerves revealed an increased thickness of the left optic nerve on both T1-weighted and T2-weighted images (Fig. 10.3). With gadolinium enhancement, there was a homogenous tubular enhancement along the left orbital optic nerve consistent with “tram-track sign.” On coronal view, there was a ring-shaped enhancement surrounding the optic axons called “doughnut sign” (Fig. 10.3). The patient had received eyeglass correction and has been followed with a stable visual acuity of 6/5 in both eyes for the past 4 years. During follow-up, OCT showed an increased thickness of the peripapillary retinal nerve finer layer (RNFL), which was stable for a long period (Fig. 10.4).

A 25-year-old male presented with complaints of retrobulbar pain in both eyes starting about 1 week ago. The pain worsened with movement of the eyes in either direction. One day after onset, the left eye became blurred, and the patient subsequently visited an ophthalmologist and was told he had disc edema. He received oral steroids 5 mg tid. However, his symptoms persisted, and he was referred to us. Ophthalmic examination showed corrected acuity of 6/6 in the right eye and CF at 10 cm in the left. Full and free range of eye movement was noted. The patient could identify 15 plates OD and only 1 plate OS using the Ishihara color test. The anterior segment was normal in both eyes, but RAPD sign was positive for the left eye. Hyperemic disc with mild blurred margin was also found in his left eye (Fig. 1.1). OCT demonstrated left disc edema with increased thickness of the peripapillary retinal nerve fiber layer (RNFL) (Fig. 1.2). Under the impression of optic neuritis, he was admitted for further examination. The patient’s peripheral blood examination showed negative findings in autoimmune and/or infectious diseases. Two days post-admission, vision in the right eye deteriorated to CF, with only one plate according to the Ishihara test. Intact peripapillary and disc capillary was found at early phase of fluorescein angiography, with dye staining on disc at late phase (Fig. 1.3). The visual field was near totally obscured (Fig. 1.4). MR imaging showed increased thickness of both optic nerves with contrast enhancement (Fig. 1.5).

A 52-year-old female presented with complaints of blurred vision OS for 2 months. She had a past medical history of peptic ulcers. She also suffered multiple skin rashes over her face (Fig. 55.1) and abdomen starting 1 year ago. Skin biopsy at another hospital showed granulomatous inflammation with mononuclear cell infiltration, which was diagnosed as sarcoidosis. She also received a chest CT scan which revealed subpleural centrilobular nodules with interstitial thickening in the left lower lobe, which was suspected to be alveolar sarcoidosis.