Choroidal vessel density in unilateral hyperopic amblyopia using en-face optical coherence tomography.

BACKGROUND: Structural changes of the choroid, such as choroidal thickening, have been indicated in amblyopic eyes with hyperopic anisometropia as compared to fellow or healthy eyes. The purpose of the present study was to investigate choroidal vascular density (CVD) in children with unilateral hyperopic amblyopia. METHODS: This study included 88 eyes of 44 patients with unilateral amblyopia due to hyperopic anisometropia with or without strabismus and 29 eyes of 29 age-matched normal controls. The CVD of Haller's layer was quantified from en-face images constructed by 3-dimensional swept-source optical coherence tomography images flattened relative to Bruch's membrane. The analysis area was a 3 × 3-mm square of macula after magnification correction. Relationships between CVD and other parameters [best-corrected visual acuity (BCVA), refractive error and subfoveal choroidal thickness (SFCT)] were investigated, and CVDs were compared between amblyopic, fellow, and normal control eyes. RESULTS: Mean CVD was 59.11 ± 0.66% in amblyopic eyes, 59.23 ± 0.81% in fellow eyes, and 59.29 ± 0.74% in normal control eyes. CVD showed a significant positive relationship with SFCT (p = 0.004), but no relationships with other parameters. No significant differences in CVD were evident among amblyopic, fellow, and normal control eyes after adjusting for SFCT (p = 0.502). CONCLUSIONS: CVD was unrelated to BCVA, and CVD did not differ significantly among amblyopic, fellow and normal control eyes. These results suggest that the local CVD of Haller's layer is unaffected in unilateral hyperopic amblyopic eyes.

Evaluation of Significance Maps and the Analysis of the Longitudinal Time Course of the Macular Ganglion Cell Complex Thicknesses in Acquired Occipital Homonymous Hemianopia Using Spectral-domain Optical Coherence Tomography.

The present study was performed to evaluate the ganglion cell complex (GCC) thickness as well as the significance map and analyse the time course of the change in GCC thickness in patients with homonymous hemianopia due to posterior cerebral artery (PCA) territory stroke using spectral-domain optical coherence tomography. This study included 40 control subjects and 11 patients with unilateral PCA territory stroke. The GCC parameters were quantified using a custom-built software programme. The GCC data, centred on the macula, was divided vertically into hemianopic and unaffected sides. GCC parameters were calculated using an average of those from both eyes. The relationship between the GCC parameters and the time after stroke was determined by regression analyses. The GCC parameters in the hemi-retinae corresponding to the affected hemifields significantly differed between the hemianopes and the control group. The area under the receiver operating characteristics curve of the GCC significance map areas was significantly high. A regression analysis revealed a significant relationship between the time after stroke and both the GCC significance map areas (r = 0.791, p = .004) and GCC thickness (r = -0.736, p = .010) on the hemianopic side. The GCC parameters on the hemianopic side were reduced in patients with acquired occipital homonymous hemianopia, and the reduction was slowly progressive probably due to transsynaptic retrograde degeneration of the retinal ganglion cells. A significance map analysis provides additional OCT parameters that could be used to investigate the effect of retrogeniculate lesions on the inner retina of patients.

Foveal avascular zone and macular vessel density after correction for magnification error in unilateral amblyopia using optical coherence tomography angiography.

BACKGROUND: To investigate the area of foveal avascular zone (FAZ) and macular vessel density (VD) after correction for magnification error in unilateral amblyopia using optical coherence tomography angiography (OCTA). METHODS: Participants comprised 15 patients with unilateral amblyopia due to anisometropia with or without strabismus (mean age, 9.8 ± 3.4 years; range, 6-17 years). OCTA images were obtained by using spectral-domain OCT with angiography software. The OCTA scanning protocol used was 3 × 3-mm volume scan centered on the fovea. OCTA images were corrected for magnification errors using individual axial length (AL), and an adjusted 2.3 × 2.3-mm square was derived as a region of interest. The FAZ area and VD in both superficial capillary plexus (SCP) and deep capillary plexus (DCP) layers, foveal minimum thickness (FMT) were assessed using built-in OCTA software and ImageJ software (NIH, Bethesda, MD). RESULTS: LogMAR in the amblyopic eyes was significantly poorer than that of the fellow eye (p < 0.001). AL was significantly shorter in the amblyopic eye than in the fellow eye (p < 0.001). FAZ area of SCP in amblyopic eyes was significantly smaller than that of fellow eyes (p < 0.001). No significant differences were seen in FAZ area of DCP, VD of SCP, VD of DCP, and FMT between amblyopic and fellow eyes (p = 0.07, 0.43, 0.55, and 0.25, respectively). CONCLUSIONS: Our present study after magnification error correction found smaller FAZ area of SCP in the amblyopic eye compared with the fellow eyes, but there was no significant difference in the macular VD between the amblyopic and fellow eyes.

Retinal Nerve Fiber Layer and Peripapillary Capillary Density Reduction Detected Using Optical Coherence Tomography Enface Images and Angiography in Optic Tract Syndrome.

In a patient with an optic tract syndrome, we describe the loss of retinal nerve fiber layer and retinal microvasculature using enface and optical coherence tomography angiography image analyses.

Effect of amblyopia treatment on choroidal thickness in hypermetropic anisometropic amblyopia using swept-source optical coherence tomography.

BACKGROUND: Recent studies using optical coherence tomography (OCT) have indicated that choroidal thickness (CT) in the anisometropic amblyopic eye is thicker than that of the fellow and normal control eyes. However, it has not yet been established as to how amblyopia affects the choroid thickening. The purpose of the present study was to investigate the effect of amblyopia treatment on macular CT in eyes with anisometropic amblyopia using swept-source OCT. METHODS: Thirteen patients (mean age: 6.2 ± 2.4 years) with hypermetropic anisometropic amblyopia were included in this study. Visual acuity (VA), axial length (AL), and CT were measured at the enrollment visit and at the final visit, after at least 6 months of treatment. CT measurements were corrected for magnification error and were automatically analyzed using built-in software and divided into three macular regions (subfoveal choroidal thickness (SFCT), center 1 mm, and center 6 mm). A one-way analysis of covariance using AL as a covariate was performed to determine whether CT in amblyopic eyes changed after amblyopia treatment. RESULTS: The average observation period was 22.2 ± 11.0 months. After treatment, VA (logMAR) improvement in the amblyopic eyes was 0.41 ± 0.19 (p < 0.001). SFCT, center 1 mm CT, and center 6 mm CT were significantly thicker in the amblyopic eyes compared with the fellow eyes both before and after treatment (p < 0.05 for all comparisons). There were no significant changes in SFCT, center 1 mm CT, or center 6 mm CT before and after treatment in the amblyopic (p = 0.25, 0.21, and 0.84, respectively) and fellow (p = 0.75, 0.84, and 0.91, respectively) eyes. The correlation between changes in logMAR versus changes in CT after treatment was not significant. CONCLUSIONS: Although VA in amblyopic eyes was significantly improved after treatment, the choroid thickening of anisometropic amblyopic eyes persisted, and there was no significant change found in the CT after the treatment. Our findings suggest that thickening of the CT in amblyopia is not directly related to visual dysfunction.

Relative Afferent Pupillary Defects in Homonymous Visual Field Defects Caused by Stroke of the Occipital Lobe Using Pupillometer.

Relative afferent pupillary defects (RAPD) may be detected in patients with occipital lobe lesions. However, no previous report has used an objective technique to record the abnormal pupillary light reflex in such cases. Therefore, we measured the pupillary light reflex objectively in 15 patients with homonymous visual field defects (HVFD) due to occipital stroke using a new pupillometer. This study detected significantly smaller and slower pupillary light reflexes in the contralateral eyes than in the other eyes, which is equivalent to the presence of RAPD in patients with HVFDs caused by retrogeniculate lesions using an objective technique. Our results confirmed those of the previous reports using the swinging flashlight test more objectively.

Macular retinal and choroidal thickness in unilateral amblyopia using swept-source optical coherence tomography.

BACKGROUND: To investigate macular retinal and choroidal thickness in amblyopic eyes compared to that in fellow and normal eyes using swept-source optical coherence tomography (SS-OCT). METHODS: This study examined 31 patients with hyperopic anisometropic amblyopia (6.9 ± 3.8 years, mean ± standard deviation), 15 patients with strabismic amblyopia without anisometropia (7.9 ± 4.2 years), and 24 age-matched controls (7.8 ± 3.3 years). Retinal and choroidal thickness was measured by 3D scans using SS-OCT. A 6-mm area around the fovea was automatically analyzed using the Early Treatment Diabetic Retinopathy Study map. The thickness from SS-OCT was corrected for magnification error using individual axial length, spherical refraction, cylinder refraction, and corneal radius. Retinal thickness was divided into the macular retinal nerve fiber layer (mRNFL), ganglion cell layer + inner plexiform layer (GCL+IPL), ganglion cell complex (GCC), and the inner limiting membrane to the retinal pigment epithelium (ILM-RPE) thickness. Retinal and choroidal thickness was compared among amblyopic, fellow, and normal eyes. RESULTS: In both amblyopia groups, there was no significant difference in the mRNFL, GCL+IPL, and GCC thicknesses among the amblyopic, fellow, and control eyes. In the anisometropic amblyopia group, choroidal thickness (subfovea, center 1 mm, nasal and inferior of the inner ring, nasal of the outer ring, and center 6 mm) of amblyopic eyes were significantly greater than that of fellow and normal eyes. In contrast, none of the choroidal thicknesses were significantly different among the investigated eyes in the strabismic amblyopia group. CONCLUSIONS: We found no significant difference in inner retinal thickness in patients with unilateral amblyopia. Although there were significant differences in choroidal thickness with hyperopic anisometropic amblyopia, there was no significant difference for the strabismic amblyopia. The discrepancy in choroidal thickness between the two types of amblyopia may be due to both differences in ocular size and underlying mechanism.

Sectoral analysis of the retinal nerve fiber layer thinning and its association with visual field loss in homonymous hemianopia caused by post-geniculate lesions using spectral-domain optical coherence tomography.

PURPOSE: To report a sectoral analysis of circumpapillary retinal nerve fiber layer (cpRNFL) thinning and its association with visual field loss using spectral-domain optical coherence tomography (SD-OCT) in patients with homonymous hemianopia following acquired post-geniculate visual pathway damage. PATIENTS AND METHODS: Seven patients with homonymous hemianopia due to unilateral acquired post-geniculate visual pathway lesions were studied. The average duration from the onset of brain lesions to the initial visit was 49.8 months. Forty-nine normal control subjects without visual field defects, as confirmed using a Humphrey visual field analyzer, were also enrolled. Measurement of the cpRNFL thickness was performed at the initial visit and 24 months using SD-OCT (RTVue-100® OCT). The cpRNFL thickness was divided into eight sectors (superior temporal: ST, temporal upper: TU, temporal lower: TI, inferior temporal: IT, inferior nasal: IN, nasal lower: NL, nasal upper: NU, superior nasal: SN). The eye on the same side as the occipital lobe lesions was defined as the ipsilateral eye, and the eye on the opposite side was defined as the contralateral eye. RESULTS: The average cpRNFL thickness in the homonymous hemianopic eyes was significantly reduced as compared with that seen in the normal controls, except for the ipsilateral eyes at the initial visit. Four of the eight sectors of the cpRNFL thickness in the homonymous hemianopic eyes were significantly reduced compared with that noted in the normal controls. In the ipsilateral eyes, the cpRNFL thickness in the ST, TU, TL, and IT sectors was significantly reduced at both the initial visit and 24 months. In the contralateral eyes, the cpRNFL thickness in the TU, TL, IT, and SN sectors was significantly reduced at both the initial visit and 24 months. The reduction of the quadrantic cpRNFL thickness significantly correlated with some of the visual field parameters, in accordance with the structure-function relationship. In the contralateral eyes, the T and I quadrant cpRNFL thickness correlated with the mean deviation and hemianopic field total deviation at 24 months. In the ipsilateral eyes, the S, T, and I quadrant cpRNFL thickness correlated with mean deviation. However, there were no correlations between the cpRNFL thickness and visual field parameters at the initial visit. CONCLUSIONS: A reduction of the cpRNFL thickness corresponding to the hemianopic visual field loss due to acquired post-geniculate visual pathway lesions was detected using SD-OCT, and the change was more evident at 24 months than at the initial visit. The latter finding suggests that this change is, at least partially, caused by transsynaptic retrograde degeneration.

Time Course of Macular and Peripapillary Inner Retinal Thickness in Non-arteritic Anterior Ischaemic Optic Neuropathy Using Spectral-Domain Optical Coherence Tomography.

To report a time course of the ganglion cell complex (GCC) and circumpapillary retinal nerve fibre layer (cpRNFL) thicknesses using spectral-domain optical coherence tomography in patients with non-arteritic anterior ischaemic optic neuropathy (NAION), five patients with unilateral NAION were studied (the average age of 66.8 ± 7.8 years old). Forty-one age-matched normal controls were also enrolled. The GCC and cpRNFL thicknesses were measured at the initial visit and at 1, 3, 6, and 12 months using RTVue-100. The GCC thickness and the cpRNFL thickness of the patients were compared with those of the normal controls. The GCC thickness in the NAION patients was 96.49 µm at the initial visit, 84.28 µm at 1 month, 74.26 µm at 3 months, 71.23 µm at 6 months, and 69.51 µm at 12 months. The values at 1, 3, 6, and 12 months were significantly reduced (p < 0.01). The cpRNFL thickness at the initial visit was significantly increased, whereas the values at 6 and 12 months were significantly reduced (p < 0.01). The GCC thickness is more useful for the detection of retinal ganglion cell loss at an early stage than the cpRNFL thickness, because the GCC thickness is unaffected by optic disc swelling at the initial visit, unlike the cpRNFL thickness.

Clinical Characteristics of Unilateral Macular Neovascularization Patients with Pachydrusen in the Fellow Eye.

Background/Objectives: To approach the clinical properties of pachydrusen that differ from conventional drusen, we investigated the incidence of macular neovascularization (MNV) in fellow eyes and the treatment outcomes of intravitreal aflibercept (IVA) in MNV eyes of unilateral MNV patients with pachydrusen in the fellow eye. Methods: We retrospectively studied 261 consecutive patients with treatment-naïve unilateral MNV. Patients were classified into four groups according to the type of drusen in the fellow eye: the pachydrusen group (n = 49), the soft drusen group (n = 63), the subretinal drusenoid deposit (SDD) group (n = 24), and the no drusen group (n = 125). The development of the MNV in the fellow eye was evaluated for five years, and the retreatment proportion after three monthly aflibercept injections was evaluated for one year. Results: The choroidal thickness in the fellow eyes and MNV eyes was the greatest in the pachydrusen group (all p < 0.001). The 5-year incidence of MNV in the pachydrusen group was similar to that in the soft drusen group and no drusen group. The pachydrusen group had a lower retreatment rate than the other groups did (pachydrusen group: 46.4%; soft drusen group: 78.1%; SDDs: 87.5%; no drusen group: 83.3%). Conclusions: Unilateral MNV patients with pachydrusen in the fellow eye had a lower retreatment rate (46.4%/1 year); therefore, aflibercept monotherapy using the PRN regimen is one of the preferred treatment methods for MNV patients with pachydrusen in the fellow eye.

The Effect of a Loading Dose Regimen in the Switch to Brolucizumab for Patients with Aflibercept-Resistant nAMD.

Purpose: To evaluate the one-year outcomes of switching to brolucizumab with and without a loading dose regimen (three monthly injections) in eyes with aflibercept-resistant neovascular age-related macular degeneration (nAMD). Methods: We retrospectively studied nAMD patients who had retinal exudate under bimonthly injections of aflibercept and were switched to brolucizumab from aflibercept. Patients were grouped into intravitreal brolucizumab injection (IVBr) with a loading dose regimen (loading group) and without a loading dose regimen (nonloading group). We assessed the best-corrected visual acuity (BCVA), central retinal thickness (CRT) at the fovea, subfoveal choroidal thickness (SFCT), IVBr status (number of injections and last injection interval), and retinal exudate status on optical coherence tomography. Results: Overall, 52 eyes received ≥1 IVBr; 26 eyes received ≥3 IVBr with 12-month follow-up. A total of 13 eyes in the loading group and 13 eyes in the nonloading group were reviewed. One year after switching, BCVA changed from 0.28 ± 0.25 to 0.19 ± 0.28 in the loading group (P=0.28) and from 0.25 ± 0.20 to 0.23 ± 0.25 in the nonloading group (P=0.92). The mean CRT decreased from 263.6 ± 40.7 µm to 221.7 ± 54.6 µm in the loading group (P=0.03), while it only changed from 244.9 ± 77.2 µm to 221.0 ± 78.7 µm in the nonloading group (P=0.26). Both the loading and nonloading groups achieved 69% dry macula. The number of injections received was significantly higher in the loading group (7.6 ± 0.6 vs. 6.8 ± 0.4, P < 0.001). Two patients (4.2%) developed intraocular inflammation. Conclusion: Switching to brolucizumab from aflibercept for eyes with nAMD with resistance to bimonthly injections of aflibercept is a valuable treatment option with and without the loading regimen. This trial is registered with UMIN000023676.

[Two cases of optic neuritis in children with rapid thinning of the ganglion cell complex].

BACKGROUND: There are many reports regarding the circumpapillary retinal nerve fiber layer (cpRNFL) in optic neuritis (ON). However, few studies of changes over time in the ganglion cell complex (GCC) have been reported. As far as we know, no studies of such changes in children have been reported. In the present study, we report two patients with pediatric ON in which the time course of GCC and cpRNFL were observed using optical coherence tomography. CASES: Two cases, one 9-year-old boy and one 11-year-old boy. The two patients showed acute visual impairment, relative afferent pupillary defect, and swelling of the optic disc, leading to the diagnosis of ON. Regardless of whether visual function was improved after steroid pulse therapy, thinning of the GCC and cpRNFL progressed rapidly over time. CONCLUSION: Atrophy of the retinal inner layer in the macula occurred soon after the onset of ON. Although the inflammation was reduced after treatment, atrophy of the ganglion cells continuted to progress. GCC thickness measurement in pediatric ON is useful for pathological assessment and followup, because we can detect atrophy of the ganglion cells and retinal nerve fibers soon after onset.

Changes in Choroidal Thickness and Structure Induced by 1% Atropine Instillation in Children With Hyperopic Anisometropic Amblyopia.

PURPOSE: To investigate the effects of 1% atropine eye drops on the choroidal thickness and structure of amblyopic and fellow eyes in children with hyperopic anisometropic amblyopia. METHODS: This study included 16 children with hypermetropic anisometropic amblyopia. All patients received 1% atropine eye drops in both eyes twice a day for 7 days. In the subfoveal choroidal region, choroidal thickness, total choroidal area, luminal area, and stromal area were measured quantitatively using swept-source optical coherence tomography. The choroidal parameters of the amblyopic and fellow eyes were compared between the baseline and atropine conditions. RESULTS: There were no significant differences in all choroidal parameters of the amblyopic eye between baseline and atropine conditions. However, the subfoveal choroidal thickness in the fellow eye was significantly higher for the atropine condition than the baseline condition. This change was accompanied by a significant increase in both the luminal and stromal areas of the choroid. The median differences of subfoveal choroidal thickness between the conditions were larger for the fellow eye (6.46%) than the amblyopic eye (0.26%). CONCLUSIONS: The choroidal structural change induced by 1% atropine instillation was smaller for the amblyopic eye than the fellow eye in children with hyperopic anisometropic amblyopia. Mechanisms of choroidal thickness changes could be inhibited in amblyopic eyes. [J Pediatr Ophthalmol Strabismus. 2023;60(1):39-45.].

Structure-function relationship between magnetic resonance imaging lesion areas and visual field defects in initial optic neuritis with altitudinal hemianopsia.

PURPOSE: To study the spatial association of magnetic resonance imaging (MRI) contrast enhancement (CE) areas with visual field defect (VFD) asymmetry in initial cases of optic neuritis (ON) with altitudinal hemianopsia (AH) with reference to nonarteritic anterior ischemic optic neuropathy (NAION) with AH. STUDY DESIGN: Multicenter, cross-sectional study. METHODS: The present study comprised 19 ON patients and 20 NAION patients with AH who underwent orbital contrast fat-suppressed MRI. The signal-to-intensity ratio (SIR) was calculated by dividing the maximum CE of the optic nerve by the mean CE of the cerebral white matter in 11 coronal sections at 3-mm intervals from immediately posterior to the eyeball to the optic chiasm. Sections in ON patients with an SIR exceeding the mean plus 2 standard deviations of the SIR at the corresponding section in the NAION group were considered abnormal. The correlation between upper-to-lower CE asymmetry in the maximum SIR section and VFD counterpart was determined. RESULTS: The ON group had significantly higher maximum SIR than that of the NAION group (1.77 ± 0.88 vs. 1.25 ± 0.32; P < .01). Seven of the 19 patients had sections with abnormally high CE extending posteriorly beyond the orbital apex. Significant spatial correspondence was observed between CE and VFD asymmetry (rs = 0.563; P = .015) in the ON group but not in the NAION group (rs = - 0. 048; P = .850). CONCLUSIONS: ON patients with AH frequently show CE even in the intracerebral optic nerve, maintaining a moderate structure-function correspondence.

Photopic negative response recorded with RETeval system in eyes with optic nerve disorders.

Electroretinography (ERG) is used to evaluate the physiological status of the retina and optic nerve. The purpose of this study was to determine the usefulness of ERGs recorded with the RETeval system in diagnosing optic nerve diseases. Forty-eight patients with optic nerve disorders, including optic neuritis, ischemic optic neuropathy, traumatic optic neuropathy, and dominant optic atrophy, and 36 normal control subjects were studied. The amplitudes of the photopic negative response (PhNR) were recorded with the RETeval system without mydriasis. The circumpapillary retinal nerve fiber layer thickness (cpRNFLT) was determined by optical coherence tomography (OCT). The significance of the correlations between the PhNR and cpRNFLT parameters were determined, and the receiver operating curve (ROC) analyses were performed for the PhNR and cpRNFLT. Patients with optic nerve disorders had significantly smaller PhNRs compared to the control subjects (P = 0.001). The ROC analyses indicated that both PhNR and cpRNFLT had comparable diagnostic abilities of detecting optic nerve disorders with PhNR at 0.857 and cpRNFLT at 0.764. The PhNR components recorded with the RETeval system have comparable diagnostic abilities as the cpRNFLT in diagnosing optic nerve disorders.

Clinical Characteristics of Neovascular Age-Related Macular Degeneration without Typical Drusen.

PURPOSE: To evaluate the clinical characteristics of neovascular age-related macular degeneration (nAMD) patients without typical drusen. METHODS: We retrospectively studied 165 eyes in 165 patients with treatment-naïve nAMD, including typical AMD and polypoidal choroidal vasculopathy (PCV). According to the fellow eye condition, the patients were divided into nAMD with and without typical drusen groups. Eyes with soft drusen or subretinal drusenoid deposits were classified into the nAMD with the typical drusen group. Smoking status and diagnoses of hypertension and diabetes were identified from hospital records and patient recall. We assessed best-corrected visual acuity (BCVA), central retinal thickness (CRT) at the fovea, subfoveal choroidal thickness (SFCT), and the number of injections received. RESULTS: The nAMD without typical drusen group was significantly younger (77.9 ± 7.6 vs. 71.8 ± 8.3, P < 0.001) and had thicker SFCT at baseline (207.9 ± 99.5 vs. 260.1 ± 113.2 µm, P=0.007) and a higher proportion of PCV (30.6 vs. 63.1%, P < 0.001). The proportion of ever-smokers was significantly higher in the nAMD without typical drusen group (54.8 vs. 70.9%, P=0.036). There were no statistically significant differences in the proportion of patients with hypertension or diabetes; BCVA, CRT, or SFCT changes; or the number of injections between the nAMD with and without typical drusen groups. CONCLUSION: The clinical features of patients in the nAMD without typical drusen group were almost identical to those of pachychoroid-driven choroidal neovascularization (CNV) patients. The nAMD without typical drusen group had a significantly higher proportion of ever-smokers than the nAMD with typical drusen group. Smoking could be a risk factor for the development of pachychoroid-driven CNV.

Input of orexin/hypocretin neurons revealed by a genetically encoded tracer in mice.

The finding of orexin/hypocretin deficiency in narcolepsy patients suggests that this hypothalamic neuropeptide plays a crucial role in regulating sleep/wakefulness states. However, very little is known about the synaptic input of orexin/hypocretin-producing neurons (orexin neurons). We applied a transgenic method to map upstream neuronal populations that have synaptic connections to orexin neurons and revealed that orexin neurons receive input from several brain areas. These include the amygdala, basal forebrain cholinergic neurons, GABAergic neurons in the preoptic area, and serotonergic neurons in the median/paramedian raphe nuclei. Monoamine-containing groups that are innervated by orexin neurons do not receive reciprocal connections, while cholinergic neurons in the basal forebrain have reciprocal connections, which might be important for consolidating wakefulness. Electrophysiological study showed that carbachol excites almost one-third of orexin neurons and inhibits a small population of orexin neurons. These neuroanatomical findings provide important insights into the neural pathways that regulate sleep/wakefulness states.

Hypothalamic orexin neurons regulate arousal according to energy balance in mice.

Mammals respond to reduced food availability by becoming more wakeful and active, yet the central pathways regulating arousal and instinctual motor programs (such as food seeking) according to homeostatic need are not well understood. We demonstrate that hypothalamic orexin neurons monitor indicators of energy balance and mediate adaptive augmentation of arousal in response to fasting. Activity of isolated orexin neurons is inhibited by glucose and leptin and stimulated by ghrelin. Orexin expression of normal and ob/ob mice correlates negatively with changes in blood glucose, leptin, and food intake. Transgenic mice, in which orexin neurons are ablated, fail to respond to fasting with increased wakefulness and activity. These findings indicate that orexin neurons provide a crucial link between energy balance and arousal.

Effects of Smoking on Outcomes of Antivascular Endothelial Growth Factor Therapy in Patients with Neovascular Age-Related Macular Degeneration Smoking and Anti-VEGF Therapy in nAMD.

PURPOSE: To evaluate the effect of smoking on the outcome of antivascular endothelial growth factor (VEGF) therapy in patients with neovascular age-related macular degeneration (nAMD). METHODS: This retrospective case-control study included 64 eyes in 59 patients with treatment-naïve nAMD. Smoking habits were obtained from hospital records and patient recall. The patients were divided into ever-smokers and never-smokers. The patients were treated with ranibizumab or aflibercept for at least 1 year. Outcome measures were best-corrected visual acuity (BCVA), central retinal thickness (CRT) at the fovea, subfoveal choroidal thickness (SCT), and number of injections received. RESULTS: There were no statistically significant differences in BCVA, CRT, or SCT changes between ever-smokers and never-smokers. The number of injections received was significantly higher in ever-smokers with a history of heavy smokers (never-smokers vs. heavy smokers: 5.3 ± 2.6/year vs. 7.3 ± 2.5/year; P=0.048 and mild smokers vs. heavy smokers: 5.2 ± 2.5/year vs. 7.3 ± 2.5/year; P=0.043). There was no significant difference in the baseline CRT or presence of atrophic retinal pigment epithelium in the fellow eyes of patients with nAMD according to smoking status; however, the baseline CRT in eyes with nAMD was significantly thinner in ever-smokers than in never-smokers (P=0.02). CONCLUSION: The anti-VEGF therapy was frequently required in nAMD patients with a history of heavy smoking. Heavy smoking could cause poor therapeutic response in nAMD patients.

Quantitative Analysis of Macular Inner Retinal Layer Using Swept-Source Optical Coherence Tomography in Patients with Optic Tract Syndrome.

OBJECTIVE: To evaluate macular inner retinal layers using swept-source optical coherence tomography (SS-OCT) in patients with homonymous hemianopia due to optic tract syndrome (OTS). METHODS: Sixteen eyes of 8 patients with OTS were studied. The macular retinal nerve fiber layer (mRNFL), ganglion cell layer and inner plexiform layer (GCL + IPL), and mRNFL and GCL + IPL (GCC) were measured by SS-OCT (DRI OCT-1 Atlantis®).The scanned area was divided into eight regions and two hemiretinae. Each retinal thickness of the OTS group was compared with that of the 25 control subjects. RESULTS: The GCC thickness in the ipsilateral eyes was significantly reduced in all regions, although predominant thinning of the GCC in the contralateral eyes was found in the nasal region. The GCC + IPL thickness was preferentially reduced at the temporal regions in the ipsilateral eyes and at the nasal regions in the contralateral eyes. The reduction rate of the GCL + IPL thickness was 29.6% at the temporal hemiretina in the ipsilateral eyes and 35.2% at the nasal hemiretina in the contralateral eyes. CONCLUSION: We found preferential loss of the GCC + IPL thickness corresponding to the hemifield defects in each eye. Quantitative analysis by SS-OCT is capable of detecting the characteristic RGC loss due to OTS.