The optic nerve head in myocilin glaucoma

PURPOSE: Approximately 1 in 30 unselected patients with open-angle glaucoma (OAG) have a mutation in the myocilin gene. The purpose of this study was to describe the morphologic features of the optic nerve head (ONH) in myocilin glaucoma. METHODS: A case-control design was adopted. Sixty-six patients heterozygous for a range of myocilin mutation (cases) were matched in disease severity to 105 patients with OAG known not to have a myocilin mutation (controls), using visual field findings. Quantifiable analysis of the ONH was undertaken of stereoscopic photographs, by using custom software with a z-screen. Subjective grading of the cup depth, lamina cribrosa pore shape and orientation, and the slope of the neuroretinal rim was performed by an examiner masked to the subject's mutation status. Mutation screening was conducted using either direct sequencing or single-stranded conformation polymorphism analysis. RESULTS: Patients with a myocilin mutation had glaucoma diagnosed earlier (P < 0.001) and had higher maximum recorded intraocular pressures (P < 0.001) than did the control OAG subjects. There was no significant (P > 0.05) difference in global disc area, global neuroretinal rim area, alpha-parapapillary atrophy, beta-parapapillary atrophy, slope of neuroretinal rim, or visible lamina cribrosa morphology between myocilin mutation carriers and patients with nonmyocilin glaucoma. Disc hemorrhages were identified more frequently in those without mutations (14/209 vs. 1/129), though this was not significant after correction for multiple hypothesis testing. CONCLUSIONS: No major structural or morphologic difference of the ONH was detected in pooled data from subjects who had myocilin mutations compared with data from individuals with nonmyocilin glaucoma.     

Changes in optic nerve head blood flow and retrobular hemodynamics following calcium-channel blocker treatment of normal-tension glaucoma

Background: Because calcium channel blockers reduce vascularresistance, they may have a clinical application in the treatment ofnormal-tension glaucoma (NTG). This study investigates changes inboth the optic disc blood flow and the hemodynamics of retrobulbarvessels in NTG patients after the systemic administration of a calcium channel blocker. Methods: Twelve eyes of 12 NTG patients (meanage 57 6 ± 15.3 years) were examined before and after a 4-weektreatment with 2 mg b.i.d. oral nilvadipine, an L-typc calcium channel blocker. By scanning laser-Doppler flowmetry (SLDF), we obtained the velocity, flow, and volume from within a 10 × 10 pixel windowplaced on the temporal rim region of the optic disc perfusion map. Byultrasound color Doppler imaging (CDI), we measured the peak systolicvelocity (PSV) and the end diastolic velocity (EDV) of the ophthalmicartery (OA), central retinal artery (CRA), nasal posterior ciliary artery (NPCA), and temporal posterior ciliary artery (TPCA). We then calculated a resistance index (RI) for each vessel. Results: After treatment, the flow and velocity of the optic disc blood flow significantly increased (P < 0.05).Nilvadipine also significantly reduced RIs of the CRA, NPCA, and TPCA(P <0 .05), and increased both the PSV of the NPCA and the EDVs of the CRA, NPCA, and TPCA. The percent change in velocity correlated significantly with the percent changes of the CRA RI and NPCA RI. Conclusions: Oral nilvadipine appears to reduce orbital vascular resistance, which consequentlyincreases the optic disc blood flow. Abbreviations.BP – blood pressure;CRA – central retinal artery;CDI – ultrasound color Doppler imaging;EDV – end diastolic velocity;NPCA – short posterior ciliary arteries located nasal to optic nerve;NTG – normal-tension glaucoma;OA – ophthalmic artery;PP – perfusion pressure;PSV – peak systolic velocity;RI – resistance index;SLDF scanning laser-Doppler flowmetry;TPCA – short posterior ciliary arteries locatedtemporal to optic nerve.     

Advances in optic nerve head analysis in glaucoma

Assessment of the optic nerve head for structural changes is critical for the detection of glaucoma and for following progression in patients with established glaucoma. Qualitative optic nerve analysis can be obtained via methods such as disc drawings and stereo disc photography. However, these methods are limited by significant interobserver and intraobserver variability. Disc photographs can also vary greatly according to the camera angle, photographic technique, lighting, and magnification. The need for accurate, reproducible, and quantitative, cost-effective techniques of assessing the optic disc and appreciation of the limitations of subjective clinical observation stimulated the development of new technologies.     

继发青光眼视乳头筛板细胞外基质的免疫组化研究

目的：用免疫组化法研究人继发青光眼乳头筛板细胞外基质的改变,探讨眼压增高对板的影响。方法：用免疫过氧化酶法（ＡＢＣ）观察７例晚期继发青光眼筛板中的Ⅳ型胶原蛋白、层连接蛋白的分布。结果：与年龄相匹配正常成人视乳头相比,继发青光眼视乳头筛板前区和筛板部Ⅳ型胶原蛋白和层连接蛋白阳性染色物明显增多,筛板后隐、重叠和融合。结论：青光眼病理过程中眼压增高引起视乳头筛板细胞外基质发生特异性改变,从而使视乳头筛板     

正常眼压性青光眼与高眼压性青光眼视神经图像分析的对比研究

目的 探讨正常眼压性青光眼 (normal-tension glaucoma, NTG)与高眼压性青光眼(high-tension glaucoma, HTG)视盘和视神经纤维层(retinal nerve fiber layer, RNFL)损害的差异。 方法 选择具有青光眼性视神经损害或RNFL缺损、相应的视野缺损的青光眼患者,NTG至少2次24 h眼压曲线和多次眼压测量均≤21 mm Hg(1 mm Hg =0.133 kPa)，HTG的眼压至少2次测量≥25 mm Hg。患者进行详细的眼科检查，同时用扫描激光偏振仪(scanning laser polarimetry, SLP)、光学相干断层扫描（optical coherence tomography, OCT）和海德堡视网膜成像仪(Heidelberg retinal tomography, HRT)定量测定视盘形态和RNFL厚度。比较两组视盘总体和相同象限测量参数。 结果 30例 NTG和 19例 HTG (共49只眼)患者的平均年龄分别为(59.6±8.6)岁(39～71岁)和(59.2±12.3)岁(36～75岁)。两组间视野缺损的平均偏差(mean deviation, MD)差异不显著(P＞0.05)。HRT测量的视盘 C/D面积比，除鼻侧象限外,NTG者视盘总体和上、下、颞侧3个象限均显著大于HTG者(P＜0.05 ),而盘缘面积小于HTG者(P＜0.05)；两组间其他视盘参数差异不显著。3种激光扫描技术所测定的总体和象限RNFL厚度，两组间差异不显著。 结论 NTG趋向大 C/D面积比和窄盘缘面积。RNFL缺损的形态分布须更精细和节段性分析。 (中华眼底病杂志, 2002, 18: 109-112)     

Mechanical environment of the optic nerve head in glaucoma

The optic nerve head (ONH) is of particular interest from a biomechanical perspective because it is a weak spot within an otherwise strong corneo-scleral envelope. The lamina cribrosa provides structural and functional support to the retinal ganglion cell axons as they pass from the relatively high-pressure environment in the eye to a low-pressure region in the retrobulbar cerebrospinal space. To protect the retinal ganglion cell axons within this unique environment, the lamina cribrosa in higher primates has developed into a complex structure composed of a three-dimensional network of flexible beams of connective tissue. The ONH is nourished by the short posterior ciliary arteries, which penetrate the immediate peripapillary sclera to feed capillaries contained within the laminar beams. This intrascleral and intralaminar vasculature is unique in that it is encased in load-bearing connective tissue, either within the scleral wall adjacent to the lamina cribrosa, or within the laminar beams themselves. Glaucoma is a multifactorial disease, and we believe that biomechanics not only determines the mechanical environment in the ONH, but also mediates IOP-related reductions in blood flow and cellular responses through various pathways. Our current understanding of the mechanical environment of the ONH is described, with particular emphasis on the influence of biomechanics in glaucoma.     

正常眼压性青光眼视盘出血与局限性视网膜神经纤维层缺损的关系

目的观察正常眼压性青光眼视盘出血与局限性视网膜神经纤维层 缺损(RNFLD)的关系。方法回顾性分析83例正常眼压性青光眼患者视盘 出血的累计发生频度及其在视盘上的分布，观察彩色立体眼底像中同一象限内的视盘出血和 视盘旁局限性RNFLD的毗邻关系及视盘出血发生之后视网膜神经纤维层的变化。结果（1）视盘出血在视盘上分布：83人中29人(34.94%)，33只眼有出血的记录， 累计58眼次，其中颞下方39眼次、颞上方14眼次、其他象限5眼次。（2）立体眼底像中同一 象限内视盘出血与视盘旁RNFLD的毗邻关系：在可获得的立体眼底像中有23眼次（15人16只 眼）视盘出血在同一象限内存在楔形RNFLD，其中22眼次出血位于视盘旁楔形RNFLD的边界附近。（3）视盘出血发生后相对应的视网膜神经纤维层的变化：24眼次出血（20人21只眼） 出血当时及出血2年以后的眼底像保存完整。随访像中原19眼次视盘出血（均位于颞下或颞上）相对应处视网膜神经纤维层发生变化，其中由无缺损到出现宽窄不一的楔形缺损者7眼次，原视盘出血毗邻的局限性RNFLD扩展者12眼次。其它5眼次视盘出血（颞上、颞下各1眼次，其他象限3眼次）随访中相对应处无明显局限性RNFLD出现。结论正常眼压性青光眼患者的视盘出血多分布于颞下，其次为颞上，视盘出血的出现常预示着其邻近部位局限性RNFLD的发生或进展。（中华眼底病杂志，2004，20：339-342）     

Quantitative evaluation of the optic nerve head in early glaucoma

AIMS—Progressive loss of neuroretinal rim tissue is known to occur early in glaucoma and measurement of the neuroretinal rim area is possible by magnification corrected analysis of optic disc photographs (planimetry). This study was performed to determine whether the facility to distinguish between glaucomatous and normal optic discs could be improved upon by: (a) taking into account the known relation between optic disc size and neuroretinal rim area, and (b) measuring rim area in a number of segments, in order to detect focal changes.
METHODS—Planimetric examination of the optic disc photographs of 88 control subjects and 51 patients with early visual field defects was performed. In the control group, multiple linear regression analysis was performed between neuroretinal rim area and optic disc area, age, sex, eye side, refraction, and keratometry. This was repeated for the whole disc and for each of twelve 30 degree segments. Normal ranges were defined by the 98% prediction intervals of the regression analysis and the sensitivity and specificity for correct identification of optic discs in the two groups determined.
RESULTS—Multiple linear regression demonstrated significant associations between the neuroretinal rim area and optic disc area and age in normal subjects. Sensitivity and specificity for glaucoma diagnosis, using the cut off derived from the 98% prediction intervals, was 37.7% and 98.9% respectively when total neuroretinal rim area alone was considered, and 88.7% and 94.3% respectively when the 30 degree segments were included. The most frequent pattern of neuroretinal rim loss was diffuse, followed by thinning in more than one sector and then by thinning in the inferotemporal sector alone.
CONCLUSIONS—This method of optic disc analysis enables the examiner to identify glaucomatous optic discs at the stage of early perimetric loss with a high degree of precision. Optic disc photography is simple, and fundus cameras are widely available. This method for glaucoma case identification may therefore be suitable for the primary care setting as well as hospital practice.

Keywords: optic disc; glaucoma; case finding; imaging     

The optic nerve head in glaucoma: role of astrocytes in tissue remodeling

Primary open angle glaucoma is a common eye disease characterized by loss of the axons of the retinal ganglion cells leading to progressive loss of vision. The site of damage to the axons is at the level of the lamina cribrosa in the optic nerve head. The mechanism of axonal loss is unknown but elevated intraocular pressure and age are the most common factors associated with the disease. Previous studies in human glaucoma and in experimental glaucoma in monkeys have established a relationship between chronic elevation of intraocular pressure and remodeling of the optic nerve head tissues known clinically as cupping of the optic disc. This review focuses on the astrocytes, the major cell type in the optic nerve head. Astrocytes participate actively in the remodeling of neural tissues during development and in disease. In glaucomatous optic neuropathy, astrocytes play a major role in the remodeling of the extracellular matrix of the optic nerve head, synthesize growth factors and other cellular mediators that may affect directly, or indirectly, the axons of the retinal ganglion cells. Due to the architecture of the lamina cribrosa, formed by the cells and the fibroelastic extracellular matrix, astrocytes may respond to changes in intraocular pressure in glaucoma, leading to some of the detrimental events that underlie axonal loss and retinal ganglion cell degeneration.     

视盘出血在正常眼压青光眼中的形态学分析

目的 对正常眼压性青光眼（NTG）患者，前瞻性评估视盘出血和视网膜神经纤维层缺损及盘周萎缩弧之间的形态学关系。 方法 患者行每月1次眼底照相，眼底立体照相和计算机图像分析系统定性及定量评估视盘出血与神经纤维层缺损及萎缩弧的关系。 结果 NTG出血组37位患者42只眼有50处眼底视盘出血，出血眼中有35只有神经纤维层缺损，发生率83.3%（35/42）。非出血组35位患者40只眼中神经纤维层局限缺损为21个，发生率52.5%（21/40），两组间神经纤维缺损发生率无统计学意义（χ2=1.403, P=0.236，P＞0.05）。出血组和非出血组两组间β区萎缩弧的发生率差异有统计学意义（χ2=7.008, P=0.008，P＜0.01)，出血组β区萎缩弧面积(2.05±0.88) mm2，非出血组β区面积(1.42±0.53) mm2，两组比较有统计学意义（t=-2.785, P=0.008）。β区萎缩弧范围在出血组：(164.00±49.87)°，非出血组(128.42±40.04)°，两组间比较有统计学意义（t=-2.618, P=0.012，P＜0.05)。随诊中出血组和非出血组盘沿丢失发生率组间比较有统计学意义（χ2=5.802, P=0.016，P＜0.01），但组间比较随诊视野损害的发生率则无统计学意义。 结论 NTG中视盘出血和神经纤维层缺损及萎缩弧之间有密切的关系。随诊中发现出血组较非出血组有更多的盘沿丢失和萎缩弧面积改变，提示NTG视盘出血是疾病进展的危险因素。 (中华眼底病杂志, 2006, 22: 232-235)     

Leber's hereditary optic neuropathy mitochondrial DNA mutations in normal-tension glaucoma

BACKGROUND: in Leber's hereditary optic neuropathy, increased optic nerve cupping has been reported by several authors. Recently, a mitochondrial DNA (mtDNA) mutation at nucleotide 11778 typically associated with Leber's hereditary optic neuropathy (LHON) was identified in a patient treated for glaucoma but lacking typical signs of LHON. The question arises: should all normal-tension glaucoma patients be further evaluated for LHON? METHODS: we screened 54 unselected patients with normal-tension glaucoma (age range 20-96 years, 16 men and 38 women) for the primary mtDNA LHON mutations at nucleotides 3460, 11778 and 14484. RESULTS: none of the patients harboured the mtDNA mutations at nucleotides 3460, 11778 or 14484 (95% confidence intervals for each mutation ranged from 0% to 5.3%). CONCLUSIONS: primary LHON mtDNA mutations are rare or absent in unselected normal-tension glaucoma patients. Therefore, unselected normal-tension glaucoma patients should not be screened for these mutations. It is probable that only normal-tension glaucoma patients with atypical features (rapid progression, early deep central scotoma, pallor of neuroretinal rim, elevated disc, peripapillary teleangiectasia) or a positive family history of visual loss compatible with a matrilinear transmission should be further evaluated.     

Pit-like changes of the optic nerve head in open-angle glaucoma.

Six patients with open-angle glaucoma and acquired pit-like changes in the optic nerve head are presented. In 1 patient evolution of the pit-like defect is documented. In all 6 patients progression of associated visual field deficits is described. It is suggested that such pit-like changes in selected patients with glaucoma may not represent congenital lesions but rather local, progressive nerve head disease, occurring particularly in response to raised intraocular pressure. The management of patients with optic nerve head pitting and the pathogenesis of glaucomatous optic neuropathy are discussed with respect to this observation.     

Detecting optic nerve head deformation and retinal nerve fiber layer thinning in glaucoma progression

The application of digital imaging technologies including confocal scanning laser ophthalmoscopy (CSLO), optical coherence tomography (OCT), and scanning laser polarimetry (SLP) has significantly improved the detection of optic nerve head (ONH) deformation and progressive retinal nerve fiber layer (RNFL) thinning for assessment of glaucoma progression. Algorithms for change analysis such as topographic change analysis and guided progression analysis perform event analysis of serial ONH surface height topology maps and RNFL thickness/RNFL retardance maps, respectively, providing a topographical display of the location of significant change. With spectral-domain OCT, it is feasible to delineate and measure the lamina cribrosa surface depth in addition to ONH surface depth and RNFL thickness. Growing evidence from experimental and clinical studies indicates that ONH and lamina cribrosa deformation can be observed prior to detectable RNFL thinning and functional loss in glaucoma. These findings lend support to the notion that upon detection of ONH/lamina cribrosa deformation, a time window for therapeutic intervention for better outcomes may exist. The ONH and the lamina cribrosa are therefore important targets for monitoring glaucoma progression. This review summarizes the latest findings comparing the performance of OCT, CSLO, and SLP for detection of progressive ONH and RNFL damages in glaucoma patients and the clinical implication and limitations of studying the morphological alteration of the ONH, lamina cribrosa, and RNFL in the assessment of glaucoma progression.     

Pressure compliance of the optic nerve head in low tension glaucoma.

Twenty eyes of 10 healthy subjects, 11 eyes of seven patients with low tension glaucoma, and three eyes of three patients with ischaemic optic neuropathy were investigated. Visual evoked responses were recorded under stepwise artificially increased intraocular pressures. The results of the visual evoked response recording (pressure compliance test) allow a clear distinction to be made between healthy subjects, patients with low tension glaucoma, and patients with ischaemic optic neuropathy. In the groups investigated a lack of autoregulation of the optic nerve head circulation was found in patients with low tension glaucoma only. Patients with anterior ischaemic optic neuropathy showed the same pressure compliance behaviour as healthy subjects. The methods used here seem to provide a practicable clinical tool in the differential diagnosis of low tension glaucoma.