Bendazac lysine in selected types of human senile cataract. A long-term double-masked placebo-controlled clinical trial with multilinear densitometric image analysis of Scheimpflug photographs

A double-masked placebo-controlled clinical trial with hard data evaluation by image analysis of Scheimpflug photographs taken at baseline and 6, 12 and 18 months after starting treatment was performed to assess the efficacy of bendazac lysine in four different types of senile cataract. The study had a classical split-plot design. For statistical evaluation, the analysis of variance and covariance for repeated measures were used for three different lens sections: anterior capsule and superficial layer, anterior cortex and nucleus. In the entire group of 53 evaluable patients (without separation into cataract-type subgroups), there was a significantly less increase over time in light scattering (i.e. film blackening) of the anterior cortex and nucleus with bendazac lysine than with placebo. There was also a strong trend in favour of the active drug at the anterior capsular level. Patients with water clefts and spokes showed a significantly less light scattering of the anterior capsule and cortex when treated with bendazac lysine. Those with nuclear changes also showed significantly less light scattering of the anterior cortex and nuclear region with the active drug than with placebo. The number of patients with subcapsular and wedge-shaped (cuneiform) cataracts was too small to be adequately assessed by statistical procedures. Nevertheless, there were indications of a beneficial effect of bendazac lysine on all the lens sections in patients with subcapsular cataracts and on the anterior cortical region in those with wedge-shaped cataracts. In conclusion, this study showed that the increase in light scattering over time, i.e. the progression of cataract, is less in bendazac lysine-treated patients than in those treated with placebo.     

Cytomorphometric study of epithelial cells in normal and cataractous human lenses in relation with hyperglycemia

The aim of the study is to evaluate and correlate the morphology and cell density of epithelial cells adhering to lens capsule surgically removed from the anterior central region with lens clarity and type of cataract present in patients with or without type 2 diabetes. Capsulorhexis specimens were obtained from patients who had undergone phacoemulsification cataract surgery. All the samples were centrifuged and stained by the aid of Papanicolaou technique and were observed under light microscope. We determinated the mean cell density, the degree of epithelial damage, and morphological indicators of cells such as cell area and the nucleus–plasma ratio. Patients with cataract demonstrated a statistical significant decrease in cell density and an heterogeneous cell picture in which enlarged cells dominated. In addition, type 2 diabetics with cataract had a significantly even lower mean epithelial cell density by the presence of larger cell area with smaller nucleus–plasma ratio. More pronounced alterations in the lens epithelium were correlated not only with the presence of cortical cataract, increased fasting blood sugar, and increased HbA1c but also with the prolonged duration of diabetes and the co-existence of diabetic retinopathy. It seems that density and morphology of the anterior lens epithelial cells determine the lens epithelium damage which is more profound in hyperglycemia and in cortical cataracts. The changes in lens epithelium seem to play an important role in cataractogenesis.     

Cataract and other ophthalmic lesions in senescence accelerated mouse (SAM). Morphology and incidence of senescence associated ophthalmic changes in mice

In a murine model of accelerated senescence (SAM), grading score and incidence in cataract, periophthalmic lesions, opacity and ulcer of the cornea were determined in mice from 4 to 24 months of age.From 4 to 6 months of age, incidence and grading score of these four categories began to increase in both the accelerated senescence prone (SAM) and resistant series with normal aging, and these increases continued with aging. As compared with the resistant series, there was a higher incidence and grading score of the four categories and a higher rate of increase in the prone series. The prone 3 series in particular showed a much higher incidence and grading score on cataract, the rate being 27·5% and 70·6% at 12 and 16 months, respectively.Histologically, the cataract was classified into two types. In one, degeneration of lens fibers, disintegration of lens cortex, and at an advanced stage, liquefaction of the lens cortex and proliferation of the anterior lens epithelial cells occurred. In the other type, lens fibers lost their distinct shapes and a homogenous mass formed at the anterior and posterior superficial cortex. The anterior lens epithelial cells had shrunk. There was an opacity and ulcer of the cornea with keratitis and the corneal epithelium was lost in case of the latter. Periophthalmic lesions included catarrhal changes of the skin of the eyelids and face and blepharitis. There were no lesions specific to each of the prone and resistant series.Thus, SAM should prove to be a suitable murine model for investigation of age-related ophthalmic lesions, including cataract in humans.     

Mitochondria of rat lenses: distribution near and at the sutures.

PURPOSE. This study is part of an effort to clarify mitochondrial distribution in the lens in order to better understand lens metabolic function. This study of the rat lens involves: 1) Using confocal microscopy, Rhodamine-123 and Calcium Green fluorescent dyes, to characterise the distribution of mitochondria and calcium in whole rat lenses of different ages in epithelial and superficial cortical fibre cells approaching sutures and 2) Using a scanning laser system to measure the optical quality at the sutures. METHODS. Lenses of rats from age 1 week to 22 months were pre-incubated for 24 hrs in 1.5 ml medium 199 (M199). Those exhibiting damage, as evaluated by protein leakage or visual opacities, were discarded. Lenses were labelled with 50 microg/ml Calcium Green for 45 min and/or 14 microM Rhodamine-123 for 25 min and embedded in 1% agarose in M199 for inverted laser scanning confocal microscopy with a 40 x water immersion lens. The lens optical properties were determined with a scanning laser system. RESULTS. Lens focal length variability significantly increased at the sutures of 13 month-old lenses, the only age investigated. An absence of both mitochondria and calcium was observed at the sutures in rat lenses of all ages. Elongated (up to 108 mm) mitochondria were present in superficial cortical fibre cells approaching the sutures of 16 month-old lenses. Calcium Green fluorescent staining was seen closer to the border of the suture, where mitochondria were absent. Along the axis, 1 week-old lenses showed a mitochondria free zone (MFZ) starting 177 microm below the lens surface, whereas in 22 month-old lenses the MFZ started only 29 microm below the surface. In the equatorial fibre cells, mitochondria were seen to a depth of 220 microm. CONCLUSIONS. Optical quality near and at the suture decreased in 13 month-old lenses despite the reduction in light scattering that should be associated with absence of mitochondria at the sutures. This suggests that mitochondrial loss in superficial cortical fibre cells may originate at the sutures and may compensate for loss of optical quality at the sutures.     

In vivo studies on cataracts using the Scheimpflug slit lamp camera

We conducted reproducibility studies on an in vivo objective method of documenting cataracts: Scheimpflug photography using the Topcon SL 45 camera. Normal and cataractous lenses were photographed and the photographs digitized and analyzed using a Perkin Elmer microdensitometer attached to a PDP 11 and Vax 11/780 computer. Linear densitometry was performed through the center of the lens. We found very good reproducibility. The intraclass correlation for the mean densities in the nucleus was 0.95: that is, intra- and interobserver variability accounted for only 5% of the overall variability. For the anterior cortex, intraclass correlation was 0.88 and for posterior cortex it was 0.84. This method may be useful, within limits, in future clinical trials of anticataract medications.     

Differences in cataractogenesis according to neodymium-YAG laser injury site]

The author examined morphological changes of the lens induced by mechanical damage with a Q-switch Nd-YAG laser (anterior capsule, anterior subcapsular deep cortex, posterior capsule). In the ruptured anterior capsule group, epithelial cell proliferation covered the ruptured capsule, and separation of posterior subcapsular sutures and swelling of the posterior subcapsular end of lens fiber cells were observed. In the ruptured subcapsular deep cortex group, swollen lens fiber cells were observed in both the anterior subcapsular and the posterior subcapsular cortex. In the ruptured posterior capsule group, the ruptured cortex was not repaired. Swollen lens fiber cells were first recognized in areas surrounding the ruptured capsule, then at the posterior side of the equator, and finally at the anterior subcapsular cortex. The continuity of the lens capsule and lens fiber cells themselves is very important part to maintain lens clarity. The destruction of this feature induced swelling of fiber cells on the opposite side of the injury area.     

Lens growth and protein density in the rat lens after in vivo exposure to ultraviolet radiation

PURPOSE: To investigate lens growth after different doses of ultraviolet radiation (UVR) and to investigate the long-term effect of a near-threshold UVR dose on the refractive index distribution in the lens. METHODS: Sprague-Dawley rats received UVR (lambda(MAX) = 300 nm) unilaterally during a 15-minute period. The exposure dose ranged from 0.1 to 20 kJ/m(2), and the rats were kept for up to 32 weeks after exposure. Intact lenses were photographed and lens wet and dry masses were measured. The protein density was estimated by quantitative microradiography. Freeze-dried lens sections were used for contact x-ray photographs. From the transmission of the microradiographs, protein density and refractive index profiles were calculated along the lens radius with a resolution of 2.5 microm. RESULTS: Lens dry mass in exposed eyes was lower than in nonexposed eyes at one week after exposure. Lens water content was decreased after low UVR doses but increased after high doses. The difference between exposed and nonexposed lenses in dry mass and water content increased with time after exposure. No significant difference was found for the mean protein density in exposed and nonexposed lenses. The protein density increased linearly in the lens cortex, from a minimum in the superficial cortex of 0.26 g/cm(3) to a maximum in the deep cortex of 0.81 g/cm(3). This corresponded to a refractive index of 1.38 and 1.48, respectively. CONCLUSIONS: Lenses exposed to UVR grew more slowly than their nonexposed contralaterals. This growth inhibition was dose dependent. Near-threshold doses led to decreased water content in the lens whereas high doses led to swelling. Six months after near-threshold UVR exposure, no global change of the refractive index was found. However, local variations of the refractive index caused a subtle cortical light scattering.     

Pyramidal anterior polar cataracts

OBJECTIVE: To document clinical features and subsequent management of pyramidal anterior polar cataracts in children. DESIGN: Retrospective, noncomparative case series and clinicopathologic correlation. PARTICIPANTS: Fifteen patients who presented to the pediatric ophthalmology clinic. INTERVENTION: All patients underwent measurement of visual acuity, assessment of ocular motility, examination of the anterior and posterior segments, and cycloplegic refraction. Amblyopia treatment was instituted when appropriate. When visual impairment occurred from cataract progression or amblyopia or both, cataract removal with or without lens implantation was performed. After surgery, correction of refractive error and treatment of amblyopia were instituted. Several pyramidal opacities were retrieved during cataract extraction and examined by light and electron microscopy. MAIN OUTCOME MEASURES: Visual acuity at initial presentation, size of lens opacity before surgery, amblyopia status, most recent visual acuity after cataract extraction, and histologic examination of lens opacity. RESULTS: Nine children had bilateral and six had unilateral pyramidal cataracts (24 eyes). There was no discernible inheritance pattern. Patients were followed for 27 months on average. Twenty of 24 eyes developed cortical opacification that extended significantly beyond the base of the pyramidal lesion. Nineteen eyes required cataract surgery: 10 eyes underwent lensectomy with anterior vitrectomy and 9 had extracapsular cataract extraction, 8 of which had insertion of a posterior chamber intraocular lens. Amblyopia was present or developed in all six patients with unilateral cataract and in eight of nine patients with bilateral cataract. Visual acuity in many eyes remained poor despite amblyopia therapy. The pyramidal opacities consisted of hyperplastic lens epithelium, which exhibited a loss of polarity and was surrounded by a collagenous matrix. CONCLUSIONS: Pyramidal anterior polar cataracts are present at birth and may represent a variant of anterior polar lens opacities. They may be unilateral or, if bilateral, they may be either symmetric or asymmetric. They consist of hyperplastic lens epithelium in a collagenous matrix. Patients with pyramidal cataracts are likely to develop amblyopia. This can result from either unilateral occurrence or asymmetry of bilateral opacities and is often worsened by surrounding cortical opacification. Many patients require cataract surgery. All infants and young children with anterior polar opacities showing this configuration should be followed for cataract progression and amblyopia.     

Effect of hyperbaric oxygen on guinea pig lens optical quality and on the refractive state of the eye

The main objective of this study was to investigate the effect of in vivo hyperbaric oxygen (HBO) treatment of albino guinea pigs on ocular refractive state and optical properties of the lens in vitro, as well as on the integrity of the mitochondria of the lens. The animals were treated 30-35 times (2.5-3 months) or 70 times (6 months) with HBO. An increased level of lens nuclear light scattering was evident by slit-lamp at 30 treatments, and this increased at 70 treatments. After 30-35 HBO treatments a myopic shift in refractive state of the eye was seen in two separate studies with two different refractionists. Also, the average back vertex distance of the lens was significantly shorter after 35 HBO treatments while spherical aberration (focal variability) increased after 70 treatments. No difference in refractive state was noted after 70 HBO treatments (a reversal of the initial myopic effect). The mitochondrial distribution and morphology of the lens epithelium and the superficial cortical fibre cells were normal after both 35 and 70 HBO treatments, highlighting that HBO treatment does not affect the superficial cortex of the lens. The results of the in vitro lens optical analysis carried out in this study correlate with the myopia observed after 30-35 HBO in vivo treatments. A similar reversible myopia and increase in lens nuclear light scattering is known to occur in humans treated with HBO for extended periods and the results suggest that the myopia was caused by a change in the refractive index of the lens. The significant loss of sharp focus after 70 HBO treatments can be correlated with previous reports of biochemical and morphological changes associated with HBO-induced loss of lens nuclear transparency in mature guinea pigs. The guinea pig HBO model may be a useful approach for the study of lens development and refractive error.     

年龄相关性白内障患者视觉质量与其晶状体区域密度的相关性

目的:研究证实Petacam系统与OQASⅡ视觉质量分析仪作为白内障客观分析仪器和帮助选择手术时机的价值.方法:研究对象为单纯年龄相关性白内障患者,排除角膜及眼底疾病,主觉验光后充分散瞳,接受OQASⅡ视觉质量分析仪测量客观散射指数(objective scatter index,OSI)及视觉质量指标调制传递函数截止频率(modulation transferfunction cut-off,MTF cut-off)值.用Pentacam系统检查测量瞳孔区前皮质、核及后囊下各区域密度.分析所得各项参数结果的相关性,并构造各个区域晶体密度与最佳矫正视力、OSI及MTF cut-off值的多元线性回归方程.结果:纳入患者69例共108眼.晶状体皮质及核的最大及平均密度均与最佳矫正视力、OSI及MTF cut-off值存在较好的相关性,且与OQAS所测得的OSI及MTF的相关性更大.通过分析所得到的多元线性回归方程,OSI是与密度相关性最大的指标,且最大密度值在各方程中占最大的影响;对于OSI和MTF,晶体核的最大密度是最重要的影响因素;同时在MTF和最佳矫正视力的影响中,皮质的混浊也占较大的比例.结论:晶体的前后皮质及晶体核,晶体任何区域的混浊都影响着视觉质量和视力.晶体核的密度在对OSI和MTF的影响中最大,皮质次之.OQASⅡ视觉质量分析仪可以作为混合性白内障客观分析仪器,其所测得的OSI是对晶体密度改变最敏感的指标,可作为辅助诊断白内障和选择手术时机的重要工具.