METTL23 mutation alters histone H3R17 methylation in normal-tension glaucoma.

Normal-tension glaucoma (NTG) is a heterogeneous disease characterized by retinal ganglion cell (RGC) death leading to cupping of the optic nerve head and visual field loss at normal intraocular pressure (IOP). The pathogenesis of NTG remains unclear. Here, we describe a single nucleotide mutation in exon 2 of the methyltransferase-like 23 (METTL23) gene identified in 3 generations of a Japanese family with NTG. This mutation caused METTL23 mRNA aberrant splicing, which abolished normal protein production and altered subcellular localization. Mettl23-knock-in (Mettl23+/G and Mettl23G/G) and -knockout (Mettl23+/- and Mettl23-/-) mice developed a glaucoma phenotype without elevated IOP. METTL23 is a histone arginine methyltransferase expressed in murine and macaque RGCs. However, the novel mutation reduced METTL23 expression in RGCs of Mettl23G/G mice, which recapitulated both clinical and biological phenotypes. Moreover, our findings demonstrated that METTL23 catalyzed the dimethylation of H3R17 in the retina and was required for the transcription of pS2, an estrogen receptor α target gene that was critical for RGC homeostasis through the negative regulation of NF-κB-mediated TNF-α and IL-1ß feedback. These findings suggest an etiologic role of METTL23 in NTG with tissue-specific pathology.

Comparison of central visual sensitivity between monocular and binocular testing in advanced glaucoma patients using imo perimetry.

BACKGROUND/AIM: This study aimed to compare central visual sensitivity under monocular and binocular conditions in patients with glaucoma using the new imo static perimetry. METHODS: Fifty-one consecutive eyes of 51 patients with open-angle glaucoma who were affected with at least one significant point in the central 10° were examined in this cross-sectional study. Monocular and binocular random single-eye tests were performed using the imo perimeter and the Humphrey field analyser (HFA) 24-2 and 10-2 tests. The eyes were assigned to 'better' and 'worse' categories based on the visual acuity and central visual thresholding. Central visual sensitivity results obtained by monocular, binocular random single-eye tests and binocular simultaneous both eye test were compared. RESULTS: The average mean deviation with the HFA 24-2 was -5.5 (-1.5, -14.6) dB (median, (IQR)) in the better eyes and -18.0 (-12.9, -23.8) dB in the worse eyes. The mean sensitivity in the central 4 points of the visual field (VF) of the worse eyes was lower when measured under the binocular eye condition than under the monocular condition. Conversely, this value of the better eyes was greater when measured under the binocular eye condition than under the monocular condition. CONCLUSIONS: The central sensitivity of the better eyes was better and that of the worse eyes poorer with binocular testing than with monocular testing in patients with glaucoma. Although monocular VF testing is still the most straightforward means to monocularly monitor glaucoma at clinical settings, binocular testing, such as provided with imo perimetry, may be a useful clinical tool to predict the effect of VF impairments on a patient's quality of visual life.

Association between axial length and in vivo human crystalline lens biometry during accommodation: a swept-source optical coherence tomography study.

PURPOSE: To evaluate the association between axial length and crystalline lens biometry with and without accommodation using the CASIA2 swept-source (SS) optical coherence tomography (OCT) system on the anterior segment. STUDY DESIGN: Intervention study. METHODS: Individuals aged 20 to 39 years were enrolled for SS-OCT imaging at 2 separate visits within 1 week. Each eye was imaged under accommodation stimuli with different amplitudes (0 D, -1 D, -3 D, -5 D, and -7 D). The anterior and posterior lens curvature radii and lens thicknesses were measured. The participants were divided into 4 groups according to axial length. RESULTS: Forty-eight participants (96 eyes) were initially enrolled. All 96 eyes were included in the analyses, as they met the eligibility criteria and each had proper OCT images. The mean participant age was 25.9 ± 4.3 years, and the mean spherical error was -3.5 ± 2.5 D. The mean axial length was 25.1 ± 1.2 mm. Multivariate analysis revealed that the anterior curvature radius became flatter and the lens thickness became thicker as the axial length increased (all P < .01). Furthermore, axial length independently contributed to the shape of the lens after adjusting for the effects of age and accommodation stimuli. CONCLUSION: Axial length was associated with lens shape after adjusting for age and accommodation stimuli. These measurements can provide a glimpse of dynamic lens biometry changes, which may help us better understand the role of lenses in various physiologic changes, including accommodation and myopia.

Electroretinograms before and after extraction of large intraocular iron foreign body.

PURPOSE: We present our findings in a case with an intraocular foreign body in which the electroretinographic (ERG) findings were useful. OBSERVATIONS: A 37-year-old man was injured by an iron fragment that penetrated into his left eye through the cornea. His visual acuity was counting fingers, and a traumatic cataract prevented an examination of the fundus. B-mode ultrasonography showed a stick-like foreign body of approximately 14 mm in length in the eye. Preoperative ERGs with a contact lens electrode showed reduced responses with many blinking artifacts. Lensectomy and pars plana vitrectomy were performed and a fragment of a wire brush was seen embedded in the superior nasal retina which was removed. The decimal visual acuity improved to 1.2 two weeks later. The postoperative ERG performed with a skin electrode showed reduced responses in the injured eye. CONCLUSIONS AND IMPORTANCE: We recommend that the physiology of the retina be assessed by recording ERGs with a skin-type electrode as soon as possible after a traumatic injury to the eye.

Evaluation of microvascular changes in the macular area of eyes with rhegmatogenous retinal detachment without macular involvement using swept-source optical coherence tomography angiography.

PURPOSE: To evaluate microvascular changes in the macular area of eyes with rhegmatogenous retinal detachment (RRD) without macular involvement (macula-on RRD) using swept-source optical coherence tomography angiography (SS-OCTA). PATIENTS AND METHODS: Five patients with macula-on RRD were eligible for analysis. All patients underwent SS-OCTA examination (Triton) for the macular area. The healthy fellow eyes were included as controls. The vessel density (VD) was calculated using binarization, and the foveal avascular zone (FAZ) was measured. The VD and FAZ area were compared between the eyes with RRD and the fellow eyes using the Wilcoxon signed rank test. RESULTS: The patients' clinical characteristics were as follows: age, 49.0 years (21.0, 54.0) (median [25, 75th percentile]); preoperative best-corrected visual acuity, -0.08 (-0.08, 0.11) for RRD and -0.08 (-0.08, -0.03) for the fellow eye (P=0.50); and axial length, 27.0 (25.1, 28.7) mm for RRD and 27.4 (25.6, 28.5) mm for the fellow eye (P=0.31). The parafoveal VD was not significantly different between the eyes with RRD and the fellow eyes (P=1.00 for the superficial retina and P=0.44 for the whole retina). The FAZ area was also similar for the eyes with RRD and the fellow eyes (P=0.31 for the superficial retina and P=0.13 for the whole retina). CONCLUSION: The findings of this study suggest that the macular microvasculature remains intact in eyes with macula-on RRD.

Optic disc vessel density in nonglaucomatous and glaucomatous eyes: an enhanced-depth imaging optical coherence tomography angiography study.

PURPOSE: To evaluate the ability of enhanced-depth imaging (EDI) optical coherence tomography angiography (OCTA) to detect vascular signals inside the glaucomatous optic disc. PATIENTS AND METHODS: Ten glaucomatous eyes of 8 subjects and 11 nonglaucomatous eyes of 7 subjects underwent EDI and conventional OCTA for optic disc analysis. The optic disc vessel density (VD) at maximum scan depth (2 mm) was compared between the 2 methods and between glaucomatous and nonglaucomatous eyes. Regression analysis was used to determine the factors affecting disc VD. RESULTS: The median (25th, 75th percentile) of the visual field mean deviation was -20.5 (-25.1, -13.5) dB in glaucoma. The disc VD measured with the EDI method was significantly greater than that measured with the conventional method in glaucoma and nonglaucoma. The disc VD was also significantly lower in glaucoma than in nonglaucoma. The disc VD and mean deviation were significantly and positively correlated in both methods (conventional: R2=0.27, EDI: R2=0.22). CONCLUSION: The correlation between disc VD and glaucoma severity was comparable between conventional and EDI measurements. Images obtained with EDI-OCTA have the additional benefit of revealing more vascular signals in deeper layers. The disc VD, as determined by both conventional and EDI-OCTA methods, may be an indicator of glaucoma severity.

The Efficacy of Transcorneal Electrical Stimulation for the Treatment of Primary Open-angle Glaucoma: A Pilot Study.

The aim of this study was to evaluate the effects of transcorneal electrical stimulation in subjects with primary open-angle glaucoma. Five eyes of four male subjects with primary open-angle glaucoma (average age: 52.25 ± 14.68 years) were enrolled. The subjects underwent transcorneal electrical stimulation every 3 months according to the following procedure. A Dawson-Trick-Litzkow electrode was placed on the cornea, and biphasic electric current pulses (10 ms, 20 Hz) were delivered using a stimulator (BPG-1,BAK Electronics) and a stimulus isolation unit (BSI-2). A current that evoked a phosphene that the subject perceived in the whole visual area was delivered continuously for 30 min. Humphrey visual field testing was performed after every third transcorneal electrical stimulation treatment. Changes in mean deviation (MD) values were evaluated with a linear regression model. Transcorneal electrical stimulation was performed 18.2 ± 9.4 times over a period of 49.8 ± 23.0 months. The average pretranscorneal electrical stimulation intraocular pressure, best corrected visual acuity, and MD values were 11.8 ± 1.79 mmHg, 0.14 ± 0.19 (logMAR) and -17.28 ± 6.24 dB, respectively. No significant differences were observed in intraocular pressure before and after transcorneal electrical stimulation. However, there was a significant positive linear relationship between changes in MD values and the number of transcorneal electrical stimulation treatments (R2 = 0.176, P = 0.005, Spearman correlation R =0.294, P = 0.008). Transcorneal electrical stimulation treatment may improve glaucomatous visual field defects in subjects with primary open-angle glaucoma. Large-scale studies are necessary to confirm these preliminary findings.

Reproducibility of Macular Vessel Density Calculations Via Imaging With Two Different Swept-Source Optical Coherence Tomography Angiography Systems.

PURPOSE: To evaluate the reproducibility of vessel density calculations using different binarization methods obtained via two commercially available swept-source optical coherence tomography angiography (SS-OCTA) systems. METHODS: Healthy volunteers were imaged using two swept-source optical coherence tomography angiography (SS-OCTA) devices, PLEXElite and Triton. SS-OCTA examinations were performed using a 3 × 3-mm volume scan pattern centered on the fovea. A total of six methods were used for binarization in ImageJ, two global thresholding and four local adaptive thresholding methods. Resultant vessel density values were compared between the instruments and binarization methods. Images for 60 eyes from 30 healthy subjects were assessed by two reviewers who were blinded to the scanning system used. RESULTS: Twenty-two eyes were excluded due to poor image quality (17 eyes from Triton, 4 eyes from PLEXElite, and 1 eye from both instruments, P = 0.003). A final 38 eyes from 23 subjects were eligible for analysis. Each binarization method and instrument led to different median values. The coefficients of variation for vessel density measurements ranged from 0.3% to 2.3% and 0.6% to 4.7% for the PLEXElite and Triton, respectively. Local adaptive thresholding methods revealed higher reproducibility than did global thresholding methods for both devices. CONCLUSIONS: Macular scans with both SS-OCTA instruments showed good reproducibility for vessel density measurements. PLEXElite recorded fewer poor images and had higher reproducibility than did Triton. These findings will inform the selection of proper binarization methods for the clinical detection of vascular diseases affecting the central retina. TRANSLATIONAL RELEVANCE: The reproducibility for macular vessel measurements with SS-OCTA instruments was good. PLEXElite recorded fewer poor images and had higher reproducibility than did Triton.

In vivo crystalline lens measurements with novel swept-source optical coherent tomography: an investigation on variability of measurement.

OBJECTIVE: To evaluate the reproducibility of in vivo crystalline lens measurements obtained by novel commercially available swept-source (SS) optical coherence tomography (OCT) specifically designed for anterior segment imaging. METHODS AND ANALYSIS: One eye from each of 30 healthy subjects was randomly selected using the CASIA2 (Tomey, Nagoya, Japan) in two separate visits within a week. Each eye was imaged twice. After image scanning, the anterior and posterior lens curvatures and lens thickness were calculated automatically by the CASIA2 built-in program at 0 dioptre (D) (static), -1 D, -3 D and -5 D accommodative stress. The intraobserver and intervisit reproducibility coefficient (RC) and intraclass correlation coefficient (ICC) were calculated. RESULTS: The intraobserver and intervisit RCs ranged from 0.824 to 1.254 mm and 0.789 to 0.911 mm for anterior lens curvature, from 0.276 to 0.299 mm and 0.221 to 0.270 mm for posterior lens curvature and from 0.065 to 0.094 mm and 0.054 to 0.132 mm for lens thickness, respectively. The intraobserver and intervisit ICCs ranged from 0.831 to 0.865 and 0.828 to 0.914 for anterior lens curvature, from 0.832 to 0.898 and 0.840 to 0.933 for posterior lens curvature and from 0.980 to 0.992 and 0.942 to 0.995 for lens thickness. High ICC values were observed for each measurement regardless of accommodative stress. RCs in younger subjects tended to be larger than those in older subjects. CONCLUSIONS: This novel anterior segment SS-OCT instrument produced reliable in vivo crystalline lens measurement with good repeatability and reproducibility regardless of accommodation stress.

Photoreceptor inner and outer segment layer thickness in multiple evanescent white dot syndrome.

PURPOSE: To evaluate the photoreceptor inner and outer segment layer thickness in eyes with MEWDS. DESIGN: Prospective, non-comparative, observational case series. The follow-up duration was 4 months. METHODS: Four women were diagnosed with unilateral MEWDS. The ages of the patients were 25, 24, 35, and 40 years. The retinal microstructure was assessed by spectral-domain optical coherence tomography (SD-OCT). The thickness of the photoreceptor inner (IS) and outer (OS) segments and sum of them (IS + OS) at the fovea were analyzed. RESULTS: The visual acuity was reduced in three of four eyes at the acute phase. SD-OCT showed that the border of IS and OS (IS/OS) line and the cone outer segment tips (COST) line in the macula area were not detected in all four eyes. The IS + OS thickness was 50.3 ± 5.6 µm and that of the healthy fellow eyes was 73.5 ± 7.0 µm (n = 4 eyes). The thickness of the IS was 27.8 ± 2.6 µm and that of the OS was 45.8 ± 7.3 µm. In all eyes, there was a spontaneous improvement of the visual acuity. SD-OCT showed a recovery of only the IS/OS line in the macular area, but the COST line was not visible in three cases. The mean IS + OS thickness increased to 56.0 ± 7.9 µm (n = 4), IS = 26.0 ± 2.0 µm (n = 3), and OS = 30.1 ± 8.7 µm (n = 3) in the early recovery phase, and to 64.8 ± 9.3 µm (n = 4), IS = 28.5 ± 1.7 µm (n = 4), and OS = 36.3 ± 7.9 µm (n = 4) in the late recovery phase. The mean inner and outer segment thickness remained unchanged in the fellow eyes. CONCLUSION: Eyes with MEWDS have changes in the photoreceptor microstructures. The change in the IS + OS thickness during the natural recovery course might be due to an increase in the OS length.

Pathological grading for predicting metastasis in phaeochromocytoma and paraganglioma.

Phaeochromocytomas (PHEO) and paragangliomas are rare catecholamine-producing tumours. Although 10-30% of these tumours metastasise, histopathological criteria to discriminate malignant from benign tumours have not been established; therefore, reliable histopathological markers predicting metastasis are urgently required. A total of 163 tumours, including 40 metastatic tumours, collected by the Phaeochromocytoma Study Group in Japan (PHEO-J) were analysed using a system called grading system for adrenal phaeochromocytoma and paraganglioma (GAPP). The tumours were scored based on GAPP criteria as follows: histological pattern, cellularity, comedo-type necrosis, capsular/vascular invasion, Ki67 labelling index and catecholamine type. All tumours were scored from 0 to 10 points and were graded as one of the three types: well-differentiated (WD, 0-2 points), moderately differentiated (MD, 3-6 points) and poorly differentiated (PD, 7-10 points). GAPP scores of the non-metastatic and metastatic groups were 2.08±0.17 and 5.33±0.43 (mean±s.e.m., P<0.001) respectively. There was a significant negative correlation between the GAPP score and the interval until metastasis (r=-0.438, P<0.01). The mean number of years until metastasis after the initial operation was 5.5±2.6 years. The study included 111 WD, 35 MD and 17 PD types. The five-year survival of these groups was 100, 66.8 and 22.4% respectively. In addition, negative immunoreactivity for succinate dehydrogenase gene subunit B (SDHB) was observed in 13 (8%) MD or PD tumours and ten of the 13 (77%) had metastases. Our data indicate that a combination of GAPP classification and SDHB immunohistochemistry might be useful for the prediction of metastasis in these tumours.

Bimatoprost ophthalmic solution 0.03% lowered intraocular pressure of normal-tension glaucoma with minimal adverse events.

PURPOSE: The aim of this study was to evaluate the efficacy and safety of bimatoprost ophthalmic solution 0.03% (bimatoprost) in Japanese normal-tension glaucoma (NTG) patients with an intraocular pressure (IOP) of 18 mmHg or less. METHODS: Bimatoprost was instilled into the unilateral conjunctival sac of Japanese NTG patients with a baseline IOP of 18 mmHg or less. The time courses of IOP, conjunctival hyperemia, superficial punctate keratitis, and adverse events were examined at 2, 4, 8, and 12 weeks post bimatoprost instillation. RESULTS: Thirty-two of the 38 enrolled NTG patients (mean age, 64.1 ± 12.6 years; 19 males and 19 females) completed the study, with six patients unable to complete the study (two patients discontinued because of side effects and four patients withdrew). The levels of IOP in the treated eyes were significantly reduced (P < 0.0001) from the baseline IOP levels. No significant change in IOP was observed in the fellow eyes. There were significant increases in conjunctival hyperemia. No significant superficial punctate keratitis scores were noted between the baseline and each point examined. Eyelash disorder, eyelid pigmentation, and deepening of the upper eyelid sulcus were observed in 28, six, and three eyes, respectively. CONCLUSION: Bimatoprost effectively lowered the IOP. It was well tolerated in Japanese NTG patients, with few patients having to discontinue because of adverse events.

Case of unilateral peripheral cone dysfunction.

PURPOSE: Peripheral cone dystrophy is a subgroup of cone dystrophy, and only 4 cases have been reported. We present a patient with unilateral peripheral cone dysfunction and report the functional changes determined by electrophysiological tests and ultrastructural changes determined by spectral domain optical coherence tomography (SD-OCT). CASE: A 34-year-old woman complained of blurred vision in both eyes. Our examination showed that her visual acuity was 0.05 OD and 0.2 OS. A relative afferent pupillary defect was present in her right eye. The results of slit-lamp examination, ophthalmoscopy, and fluorescein angiography were normal except for pallor of the right optic disc. SD-OCT showed a diffuse thinning of the retina in the posterior pole of the right eye. A severe constriction of the visual fields was found in both eyes but more in the right eye. The photopic full-field electroretinograms (ERGs) were reduced in the right eye but normal in the left eye. The multifocal ERGs were severely reduced throughout the visual field except in the central area of the right eye. The multifocal ERGs from the left eye were normal. The pattern visual evoked responses were within the normal range in both eyes. She had a 5-year history of sniffing paint thinner. RESULTS: Although the visual dysfunction was initially suspected to be due to psychological problems from the results of subjective tests, objective tests indicated a peripheral cone dysfunction in the right eye. The pathophysiological mechanism and the relationship with thinner sniffing were not determined. CONCLUSIONS: Our findings indicate that peripheral cone dysfunction can occur unilaterally. Electrophysiology and SD-OCT are valuable tests to perform to determine the pathogenesis of unusual ocular findings objectively.

[Effects of vitrectomy as a treatment for proliferative diabetic retinopathy in young patients].

PURPOSE: To investigate the effects of vitrectomy as a treatment for the proliferative diabetic retinopathy (PDR) in patients under 40 years old. METHODS: Sixty eyes of 37 patients under 40 years old with PDR who had undergone vitrectomy for the first time in Juntendo University Urayasu Hospital were included in this study. Preoperative condition, operation methods, visual acuity after operation and complications both during or after operation, especially neovascular glaucoma (NVG), were reviewed retrospectively. RESULTS: Visual acuity improved in 43 eyes (72%) by more than 0.2 logMAR compared to that before the operation, remained stable in 4 eyes (6%) and deteriorated in 13 eyes (22%) by more than 0.2 logMAR compared to that before operation. Optic atrophy and phthisis caused by NVG constituted 69% of the causes of complicated final visual acuity. Male patients and patients who had both hypertension and proteinuria had significantly higher prevalence of NVG after vitrectomy (p < 0.05), and patients who retained their lens after the first vitrectomy had a significantly lower prevalence of NVG after the operation (p < 0.05). CONCLUSIONS: In young PDR patients under 40 years old, postoperative NVG was the main reason for severe visual impairment. Multifactorial causes, both general and ophthalmic seem to be implicated in the onset and progression of NVG derived from PDR.

[Degeneration of ponto-cerebellar tract visualized by diffusion tensor imaging in multiple system atrophy].

We visualized ponto-cerebellar tracts projecting through the middle cerebellar peduncle of 3 patients with early stage multiple system atrophy (MSA), 3 patients with advanced stage MSA, and a healthy control using diffusion tensor imaging (DTI) on 1.5T magnetic resonance imaging (MRI). We also examined whether the location of the degenerated ponto-cerebellar tracts coincided with that of the transverse part of the so-called "hot cross bun sign (HCB)" on MRI. DTI successfully demonstrated the degeneration of ponto-cerebellar tracts in MSA patients. The tracts in advanced stage MSA patients appeared more sparse than those in patients of the early stage. High apparent diffusion coefficient (ADC) values and low fractional anisotropy (FA) values also indicated the degeneration of the ponto-cerebellar tracts in MSA patients. The tracts in the ventral pons were more sparse than those in the central pons. The location of the degenerated ponto-cerebellar tracts of the central pons appeared to coincide with that of the transverse part of HCB. Visualization of degenerated ponto-cerebellar tracts that cross the ventral pons using DTI might be useful for the early diagnosis.

Increased serum total antioxidant status and decreased urinary 8-hydroxy-2'-deoxyguanosine levels in patients with normal-tension glaucoma.

PURPOSE: To investigate the amount of systemic oxidative stress-related DNA damage and serum total antioxidant status of patients with normal-tension glaucoma compared with healthy controls. METHODS: Forty-three patients with normal-tension glaucoma selected from 60 consecutive newly diagnosed patients with primary open-angle glaucoma were enrolled. Each patient's intraocular pressure (IOP) was measured seven times over a 24-hour period. Those whose highest IOP was over 21 mmHg were excluded. Forty control subjects were recruited. The serum total antioxidant status was assessed colorimetrically by its ability to reduce the generation of the radical cation ABTS (2,2-azinobis-3-ethylbenzthiazoline sulphonate). The urinary 8-hydroxy-2'-deoxyguanosine was measured as a marker of oxidative DNA damage and normalized to creatinine. The results were compared between healthy subjects and patients with normal-tension glaucoma. RESULTS: The control and normal-tension glaucoma groups did now show significant differences for age, gender, serum fructosamine, cholesterol and triglyceride levels; systolic and diastolic blood pressure, body mass index; and prevalence of hypertension. The serum total antioxidant status was significantly higher (p = 0.01) and the urinary 8-hydroxy-2'-deoxyguanosine/creatinine level significantly lower (p = 0.03) in the patients with normal-tension glaucoma compared with the controls. Even after we adjusted the data for independent variables, the incidence of normal-tension glaucoma was significantly correlated with high serum total antioxidant levels (p = 0.03; odds ratio, 1.007; 95% confidence interval, 1.001-1.013) and low urinary 8-hydroxy-2'-deoxyguanosine/creatinine (p = 0.02; odds ratio 0.76; 95% confidence interval, 0.61-0.96). CONCLUSIONS: Increased serum total antioxidant and decreased 8-hydroxy-2'-deoxyguanosine may reflect compensatory alterations in response to increased systemic oxidative stress in patients with normal-tension glaucoma.

Mutant WDR36 directly affects axon growth of retinal ganglion cells leading to progressive retinal degeneration in mice.

Primary open-angle glaucoma (POAG) is one of the three principal subtypes of glaucoma and among the leading cause of blindness worldwide. POAG is defined by cell death of the retinal ganglion cells (RGCs) and surrounding neuronal cells at higher or normal intraocular pressure (IOP). Coded by one of the three genes responsible for POAG, WD repeat-containing protein 36 (WDR36) has two domains with a similar folding. To address whether WDR36 is functionally important in the retina, we developed four transgenic mice strains overexpressing a wild-type (Wt) and three mutant variants of D606G, deletion of amino acids at positions 605-607 (Del605-607) and at 601-640 (Del601-640) equivalent to the location of the D658G mutation observed in POAG patients. A triple amino acid deletion of mouse Wdr36 at positions 605-607 corresponding to the deletion at positions 657-659 in humans developed progressive retinal degeneration at the peripheral retina with normal IOP. RGCs and connecting amacrine cell synapses were affected at the peripheral retina. Axon outgrowth rate of cultured RGC directly isolated from transgenic animal was significantly reduced by the Wdr36 mutation compared with Wt. Molecular modeling of wild and mutant mouse Wdr36 revealed that deletion at positions 605-607 removed three residues and a hydrogen bond, required to stabilize anti-parallel ß-sheet of the 6th ß-propeller in the second domain. We concluded that WDR36 plays an important functional role in the retina homeostasis and mutation to this gene can cause devastating retinal damage. These data will improve understanding of the functional property of WDR36 in the retina and provide a new animal model for glaucoma therapeutics.

Alternative approach to treating malignant glaucoma after trabeculectomy with unplanned zonulectomy.

PURPOSE: To report the role of Healon5 injection combined with medications in patient with malignant glaucoma after trabeculectomy with unplanned zonulectomy. METHODS: Two days after trabeculectomy with unplanned zonulectomy for neovascular glaucoma in an eye with diabetic retinopathy, a patient developed malignant glaucoma due to the ciliovitreal block caused by the vitreous herniation through the peripheral iridectomy to the limbal incision with flat bleb and anterior chamber, and the intraocular pressure was elevated to 33 mmHg. The medications for the management of malignant glaucoma failed to relieve the malignant mechanism, and Healon5, a viscoadaptive, viscoelastic, and ophthalmic viscosurgical device, was injected through a paracentesis until the anterior chamber became deep enough to block the vitreous herniation to the limbal incision. RESULTS: After Healon5 injection, the intraocular pressure was reduced enough that the bleb was re-formed, and the anterior chamber remained deep, even without medication. CONCLUSIONS: In patients presenting with malignant glaucoma after trabeculectomy with unplanned zonulectomy, Healon5 injection, combined with medications, may be a safe and effective approach before performing vitrectomy.

Elevated serum immunoglobulin G titers against Chlamydia pneumoniae in primary open-angle glaucoma patients without systemic disease.

PURPOSE: To determine if Chlamydia pneumoniae infection is associated with primary open-angle glaucoma (POAG). PATIENTS AND METHODS: Consecutive patients with newly diagnosed primary POAG attending the Glaucoma clinic of Keio University Hospital between June 2007 and January 2008 were considered for inclusion in this prospective case-control study. Forty consecutive POAG patients and 41 normal healthy individuals as a control population met the inclusion criteria. The exclusion criteria for both groups were; taking steroids or immunosuppressive agents, smoking, and history of any acute or chronic systemic disease including stroke, heart attack, diabetes mellitus, hypertension, asthma, and autoimmune diseases. The serum was analyzed for C. pneumoniae and C. trachomatis immunoglobulin G antibody titers by enzyme-linked immunosorbent assay. Seroactivity to each antigen between case and control groups was evaluated by Mann-Whitney U test. RESULTS: The age, male/female ratio, and intraocular pressure of the cases and control groups were not significantly different. Immunoglobulin G titers for C. pneuemoniae was significantly higher in patients with POAG than in controls (P=0.009). The titers to C. trachomatis were not significantly different between the 2 groups (P=0.99). CONCLUSION: The results suggest that higher C. pneumoniae titers are associated with POAG. If confirmed, this may indicate either a common factor that causes susceptibilities to both glaucoma and C. pneumoniae infection or that C. pneumoniae may be a causal factor for developing POAG.

Serum free fatty acids levels not associated with normal tension glaucoma.

PURPOSE: To determine the free fatty acid levels in the sera of patients with normal-tension glaucoma and compare it with that of normal controls. METHODS: Forty-four consecutive patients with newly diagnosed normal-tension glaucoma and forty-four age and gender matched controls were evaluated. The type and level of fatty acids in the sera were measured by gas chromatography (Model GC17A; Shimazu, Kyoto, Japan). Twenty-four fatty acids were identified from 12:0 to 24:1. The values were compared between the normal-tension glaucoma and control groups by Mann-Whitney U tests. RESULTS: No statistically significant difference was found in the levels of any free fatty acids between the normal-tension glaucoma group and control group. CONCLUSION: No significant association was found in the serum free fatty acids levels including docosahexaenoic acid and eicosapentaenoic acid between normal-tension glaucoma patients and controls.