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Background/aimsMeibomian gland dysfunction (MGD) is the most common form of evaporative dry eye disease, but its pathogenesis is poorly understood. This study examined the histopathological features of meibomian gland (MG) tissue from cadaver donors to identify potential pathogenic processes that underlie MGD in humans.MethodsHistological analyses was performed on the MGs in the tarsal plates dissected from four cadaver donors, two young and two old adults, including a 36-year-old female (36F) and three males aged 30, 63 and 64 years (30M, 63M and 64M).ResultsThe MGs of 36F displayed normal anatomy and structure, whereas the MGs of 30M showed severe ductal obstruction with mild distortion. The obstruction was caused by increased cytokeratin levels in association with hyperproliferation, but not hyperkeratinisation. In two older males, moderate to severe MG atrophy was noted. Cell proliferation was significantly reduced in the MG acini of the two older donors as measured by Ki67 labelling index (6.0%±3.4% and 7.9%±2.8% in 63M and 64M, respectively) when compared with that of the two younger donors (23.2%±5.5% and 16.9%±4.8% in 30M and 36F, respectively) (pConclusionOur histopathological study, based on a small sample size, suggests potentially distinct pathogenic mechanisms in MGD. In the young male adult, hyperproliferation and aberrant differentiation of the central ductal epithelia may lead to the obstruction by overproduced cytokeratins. In contrast, in older adults, decreased cell proliferation in acinar basal epithelia could be a contributing factor leading to MG glandular atrophy.

PURPOSE: To investigate correlations of oxygen (pO(2)) in the ocular anterior segment of human eyes and aqueous humor antioxidant levels of ascorbate (AsA) and total reactive antioxidant potential (TRAP) with glaucoma and vitreous status. METHODS: This prospective, cross-sectional study stratified patients (n=288 eyes) by lens and vitreous status and presence of primary open angle glaucoma for statistical analyses. Intraocular pO(2) measurements with a fiberoptic probe were made in patients at the beginning of planned glaucoma and/or cataract surgery. Aqueous humor specimens were obtained for antioxidant analysis (AsA, TRAP). RESULTS: Following prior pars plana vitrectomy, pO(2) was significantly higher compared to the reference group (cataract; CAT) in the anterior chamber (AC) angle (16.2 ± 5.0 vs. 13.0 ± 3.9 mmHg, P=.0171) and in the posterior chamber (7.6 ± 3.1 vs. 3.9 ± 2.7 mmHg, P

Background/aimsWe wished to determine whether the pupillary light reaction can differentiate preclinical Alzheimer’s disease (AD) subjects from normal ageing controls. We performed a prospective study evaluating the pupillary light reaction in a cohort of well-characterised subjects with preclinical AD versus normal ageing controls.MethodsWe recruited 57 subjects from our institution’s Memory and Aging Project, part of our Alzheimer’s Disease Research Center. All subjects completed PET-PiB imaging, cerebrospinal fluid analysis and at least 1 neuropsychiatric assessment after their baseline assessment. All participants were assigned a clinical dementia rating and underwent a complete neuro-ophthalmic examination. Participants were divided into a dementia biomarker+ (preclinical AD) and biomarker– (normal ageing) group based on preclinical risk for Alzheimer’s dementia. Pupillometry measurements were performed by using the NeurOptics PLR-200 Pupillometer.ResultsA total of 57 subjects were recruited with 24 dementia biomarker+ and 33 dementia biomarker- individuals. A variety of pupil flash response (PLR) parameters were assessed. Comparisons between groups were analysed using generalised estimating equations. None of the pupillary parameters showed a significant difference between groups.ConclusionsWe found no significant differences in PLR between preclinical AD subjects and normal ageing controls. This suggests that the disease effect on the PLR may be small and difficult to detect at the earliest stages of the disease. Future studies could include larger sample size and chromatic pupillometry.

Oxygen levels in the eye are generally low and tightly regulated. Oxygen enters the eye largely by diffusion from retinal arterioles and through the cornea. In intact eyes, oxygen from the retinal arterioles diffuses into the vitreous body. There is a decreasing oxygen gradient from the retina to the lens, established by oxygen consumption by ascorbate in the vitreous fluid and lens metabolism. Age-related degeneration of the vitreous body or removal during vitrectomy exposes the posterior of the lens to increased oxygen, causing nuclear sclerotic cataracts. Lowering oxygen in the vitreous, as occurs in patients with ischemic diabetic retinopathy, protects against cataracts after vitrectomy. Vitrectomy and cataract surgery increase oxygen levels at the trabecular meshwork and with it the risk of open angle glaucoma. Two additional risk factors for glaucoma, African heritage and having a thinner cornea, are also associated with increased oxygen in the anterior chamber angle. Preservation of the vitreous body and the lens, two important oxygen consumers, would protect against nuclear sclerotic cataracts and open angle glaucoma. Delaying removal of the lens for as long as possible after vitrectomy would be an important step in delaying ocular hypertension and glaucoma progression.

Glaucoma is the second leading cause of blindness worldwide. Physicians often use surrogate endpoints to monitor the progression of glaucomatous neurodegeneration. These approaches are limited in their ability to quantify disease severity and progression due to inherent subjectivity, unreliability, and limitations of normative databases. Therefore, there is a critical need to identify specific molecular markers that predict or measure glaucomatous neurodegeneration. Here, we demonstrate that growth differentiation factor 15 (GDF15) is associated with retinal ganglion cell death. Gdf15 expression in the retina is specifically increased after acute injury to retinal ganglion cell axons and in a murine chronic glaucoma model. We also demonstrate that the ganglion cell layer may be one of the sources of secreted GDF15 and that GDF15 diffuses to and can be detected in aqueous humor (AH). In validating these findings in human patients with glaucoma, we find not only that GDF15 is increased in AH of patients with primary open angle glaucoma (POAG), but also that elevated GDF15 levels are significantly associated with worse functional outcomes in glaucoma patients, as measured by visual field testing. Thus, GDF15 maybe a reliable metric of glaucomatous neurodegeneration, although further prospective validation studies will be necessary to determine if GDF15 can be used in clinical practice.

Previous studies reported that characteristic lens opacities were present in Alzheimer Disease (AD) patients postmortem. We therefore determined whether cataract grade or lens opacity is related to the risk of Alzheimer dementia in participants who have biomarkers that predict a high risk of developing the disease. AD biomarker status was determined by positron emission tomography-Pittsburgh compound B (PET-PiB) imaging and cerebrospinal fluid (CSF) levels of Aβ42. Cognitively normal participants with a clinical dementia rating of zero (CDR=0; N=40) or with slight evidence of dementia (CDR=0.5; N=2) were recruited from longitudinal studies of memory and aging at the Washington University Knight Alzheimer's Disease Research Center. The age, sex, race, cataract type and cataract grade of all participants were recorded and an objective measure of lens light scattering was obtained for each eye using a Scheimpflug camera. Twenty-seven participants had no biomarkers of Alzheimer dementia and were CDR=0. Fifteen participants had biomarkers indicating increased risk of AD, two of which were CDR=0.5. Participants who were biomarker positive were older than those who were biomarker negative. Biomarker positive participants had more advanced cataracts and increased cortical light scattering, none of which reached statistical significance after adjustment for age. We conclude that cataract grade or lens opacity is unlikely to provide a non-invasive measure of the risk of developing Alzheimer dementia. Key Words: Lens opacity, cataract, Scheimpflug imaging, Alzheimer disease biomarkers, preclinical Alzheimer disease

To evaluate the safety of intravitreal injection of bevacizumab in rabbits using electrophysiological testing and histopathologic analysis.New Zealand albino rabbits were injected in one eye with control antibody (n = 2), 0.05 mL of bevacizumab (n = 3), or 0.2 mL of bevacizumab (n = 3). Electroretinograms were obtained 1 week and 4 weeks after injection. Histologic analysis was performed after completion of the electroretinographic studies.No statistical differences were seen in scotopic and photopic a- and b-wave amplitudes between untreated control and bevacizumab-injected eyes. No histopathologic differences were identified between untreated control and bevacizumab-injected eyes.Our study did not find evidence of retinal toxicity from a single intravitreal injection of bevacizumab in rabbits.

To report intraocular oxygen tension in eyes of diabetic and nondiabetic patients.A prospective, interventional consecutive case series.Oxygen was measured with an optical oxygen sensor in patients who were undergoing vitrectomy. Before turning on the infusion fluid, intraocular oxygen tension was measured in two locations: adjacent to the lens and in the mid vitreous cavity.Fifty eyes from 50 patients were included in the study. Twenty-one eyes were from diabetic patients and 29 eyes were from nondiabetic patients. The mean oxygen tension adjacent to the lens was significantly lower in diabetic than in nondiabetic patients (8.4 +/- 0.7 mm Hg vs 10.7 +/- 0.8 mm Hg; P.05). Similarly, the mean oxygen tension in the center of the vitreous cavity was lower in diabetic than in nondiabetic patients (5.7 +/- 0.7 mm Hg vs 8.5 +/- 0.6 mm Hg; P.001). In subgroup analyses, previous panretinal photocoagulation or cataract surgery did not affect oxygen levels significantly in the vitreous of diabetic or nondiabetic patients.Eyes from diabetic patients have significantly lower intraocular oxygen tension than in eyes from nondiabetic patients. Because oxidative damage to the lens nucleus and increased intraocular oxygen tension have been associated with nuclear sclerotic cataract, these findings may help explain recent reports of an apparent protective effect of diabetes mellitus against nuclear sclerotic cataract.

This study evaluated in vivo imaging capabilities and safety of qualitative monitoring of oxygen saturation of hemoglobin (sO_2) of rabbit ciliary body tissues obtained with acoustic resolution (AR) photoacoustic tomography (PAT). AR PAT was used to collect trans-scleral images from ciliary body vasculature of seven New Zealand White rabbits. The PAT sO_2 measurements were obtained under the following conditions: when systemic sO_2 as measured by pulse oximetry was between 100% and 99% (level 1); systemic sO_2 as measured by pulse oximetry was between 98% and 90% (level 2); and systemic sO_2 as measured by pulse oximetry was less than 90% (level 3). Following imaging, histological analysis of ocular tissue was conducted to evaluate for possible structural damage caused by the AR PAT imaging. AR PAT was able to resolve anatomical structures of the anterior segment of the eye, viewed through the cornea or anterior sclera. Histological studies revealed no ocular damage. On average, sO_2 values (%) obtained with AR PAT were lower than sO_2 values obtained with pulse oximetry (all p < 0.001): 86.28 ± 4.16 versus 99.25 ± 0.28, 84.09 ± 1.81 vs. 95.3 ± 2.6, and 64.49 ± 7.27 vs. 71.15 ± 10.21 for levels 1, 2 and 3 respectively. AR PAT imaging modality is capable of qualitative monitoring for deep tissue sO_2 in rabbits. Further studies are needed to validate and modify the AR PAT modality specifically for use in human eyes. Having a safe, non-invasive method of in vivo imaging of sO_2 in the anterior segment is important to studies evaluating the role of oxidative damage, hypoxia and ischemia in pathogenesis of ocular diseases.

Purpose The purpose of this study is to evaluate effects of vitrectomy (PPV) and lens extraction with intraocular lens implantation (PE/IOL) on molecular oxygen (pO2) distribution, aqueous humor antioxidant-oxidant balance, aqueous humor dynamics, and histopathologic changes in the trabecular meshwork (TM) in the older macaque monkey. Methods Six rhesus monkeys underwent PPV followed by PE/IOL. pO2, outflow facility, and intraocular pressure (IOP) were measured. Aqueous and vitreous humor specimens were analyzed for antioxidant status and 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative damage. TM specimens were obtained for immunohistochemical and quantitative PCR analysis. Results pO2 at baseline revealed steep gradients in the anterior chamber and low levels in the posterior chamber (PC) and around the lens. Following PPV and PE/IOL, pO2 significantly increased in the PC, around the IOL, and angle. IOP increased following both surgical interventions, with no change in outflow facility. Histopathologic analysis did not show changes in TM cell quantification, but there was an increase in 8-OHdG. Quantitative PCR did not reveal significant differences in glaucoma-related gene expression. Aqueous and vitreous humor analysis revealed decreased ascorbate and total reactive antioxidant potential and increased 8-OHdG in the aqueous humor only in the surgical eyes. Conclusions Oxygen distribution in the older rhesus monkey is similar to humans at baseline and following surgical interventions. Our findings of histopathologic changes of TM oxidative damage and alterations in the oxidant-antioxidant balance suggest a potential correlation of increased oxygen exposure with oxidative stress/damage and the development of open angle glaucoma.

Purpose To measure oxygen (pO 2 ) in eyes of patients undergoing intraocular surgery and identify correlations with central corneal thickness (CCT). Design Prospective, cross-sectional study. Methods setting: Institutional. patient population: 124 patients undergoing cataract and/or glaucoma surgery. observation procedure: Prior to surgery, an oxygen sensor was introduced into the anterior chamber (AC) via peripheral corneal paracentesis. The tip of the flexible fiberoptic probe was positioned for 3 measurements in all patients: (1) near central corneal endothelium; (2) in mid-AC; and (3) in AC angle. In patients undergoing cataract extraction, additional measurements were taken (4) at the anterior lens surface and (5) in the posterior chamber. main outcome measures: pO 2 measurements at 5 locations within the eye were compared to central corneal thickness measurements by multivariate regression analyses. Results There was a statistically significant inverse correlation between CCT and pO 2 in the anterior chamber angle ( P = .048). pO 2 was not significantly related to CCT at any other location, including beneath the central cornea. Regression analysis relating CCT to age, race, and oxygen levels in all 5 locations in the anterior segment revealed an association of a thinner cornea with increasing age ( P = .007). Conclusions Physiologic correlations with central corneal thickness may provide clues to understanding why a thinner cornea increases the risk of open glaucoma. Associations between glaucoma risk, CCT, and pO 2 in the AC angle suggest that exposure of the outflow system to increased oxygen or oxygen metabolites may increase oxidative damage to the trabecular meshwork cells, resulting in elevation of intraocular pressure.

As recently as two decades ago, textbooks on vitreous taught students of ophthalmology that the vitreous gel had no real function in the adult eye other than to serve as a space-occupying, optically clear structure. In fact, one such textbook published in 1994 stated, “Apart from its role in oculogenesis, the vitreous has no well substantiated function so that an eye devoid of gel is not adversely affected” [1]. However, beginning in 2005 with published reports of oxygen tension measurements in the human vitreous gel before and after vitrectomy surgery [2] and culminating with reports in 2009 that the human vitreous gel consumes oxygen in an ascorbate-dependent manner [3], a new understanding of the vitreous gel and its role in vitreoretinal physiology and pathology has emerged.

Purpose: To conduct an epidemiological survey of cataracts and examine the characteristics of lens opacities in Chinese Singaporeans. The results are then compared with those from two similar surveys previously done in Japan in Noto Area, Honshu, and Amami, Kyushu, respectively.Subjects and Methods: 468 subjects of*50 years of age, who responded to the invitation to participate, were examined. Examination principally included photo-documentation of the anterior and posterior segments of both eyes. Evaluation and grading of lens opacities were done using graphical analysis of Scheimpflug and retro-illumination images. Inter-group comparisons were based on statistical analysis of cataract prevalence and distribution.Results: The prevalence of clear lenses decreased with aging with no significant difference between males and females - a finding common to Singapore and the two Japanese study groups. The prevalence of cataracts (or lens opacities of Grade II and above) in 60-79 year-old Singapore subjects was significantly higher than Noto and Amami subjects in the same age group. Further, cortical opacity was the main type in Singapore subjects in their 50s and which was significantly higher than Noto subjects of the same age group. In all age groups, the distribution and prevalence of both nuclear and subcapsular types in the Singapore group were higher than the two Japanese study groups.Conclusions: Cataracts in Chinese Singaporeans are characterized by a high prevalence of nuclear opacities which was generally seen in tropics and sub-tropics. Our study also suggested the involvement of solar-UV in cortical cataracts as well as that of additional risk factors, such as environmental temperature and race, in nuclear and subcapsular cataract formation.J Epidemiol, 2001 ; 11 : 16-23

UV irradiation has the potential to induce the development of lens opacities. This has been demonstrated since long with animal experiments. Unfortunately these animal cataracts did not explain or elucidate the epidemiological observation that the frequency of human cataracts--such as the so called senile cataract--is remarkably higher in regions with increased cosmic UV irradiation or in the population being in close professional contact with UV-irradiation. The main problem was that the type of UV induced animal cataracts differs remarkably with respect to onset, localization of the opacity, size and its timely progression from the cataract classes observed in human. The research of the last 10 years comes to the conclusion that beside the direct (acute) damage--as seen in animal studies due to high UV dosages--we have to realize a syn- or co-cataractogenic potential of UV irradiation even below the threshold dose which is able to accumulate in the lens and to initiate together with other risk factors (chronic damage) the opacification of the lens. The mechanism for the animal cataract and the human cataract (with an UV risk participation) are different. The epidemiological research about cataract frequency in different regions of the world have to take into account that UV irradiation--even below a threshold dose--is a possible risk among the multifactorial pathogenesis of human cataract.

Cataract epidemiological surveys applying objective judgement through lens images in the climatically different places of Noto and Amami, Japan, Singapore and Reykjavik, Iceland yielded several significant results about the influence of solar UV. 1) The percentage of transparent and of lens opacification was significantly higher in the Reykjavik subjects than in the Singaporeans. 2) The percentages including early changes were higher in Amami and Singapore than in Noto and Reykjavik. 3) Progressed lens opacification was highest in Singapore. While the main type of lens opacification was cortical in Noto and Reykjavik, that of Singapore was nuclear. 4) A significant correlation between cortical opacification and the history of time spent outdoors was noticed. The UV risk for formation and/or progression of cortical opacification should be acceptable from the epidemiological standpoint. J Epidemiol, 1999; 9 : S33-S38.

In order to induce experimental steroid cataracts in rat eyes similar morphologically to those seen in human eyes, prednisolone acetate was administered either topically or systemically for 12 months with a low dose of X-irradiation as a cocataractogenic factor. Twenty-seven Brown-Norway rats were randomly divided into a control group (group I) with no steroid administration; an eyedrop group (group II) with a daily 1% prednisolone acetate instillation of a total volume of 1.0 mg/kg in both eyes, and a systemic group (group III) with a daily intramuscular injection of 0.8-1.0 mg/kg prednisolone acetate. The right eyes of animals in each group were X-irradiated with a single dose of 2 Gy. Topical and systemic steroid administrations started 2 weeks after X-irradiation. Anterior segment changes were documented with a slitlamp microscope and an anterior eye segment analysis system once a month. Body weight and blood glucose levels were examined every week and every 2 weeks, respectively. The mortality rates in groups I, II and III were 0, 11 (1/9) and 25% (3/12), respectively. The both lenses in group I showed a gradual increase in light-scattering intensity in the nuclear and supranuclear regions over time. Initial lens changes in both steroid-treated groups were Y-suture dissociation and a slight increase in light-scattering intensity in the posterior supranuclear region 3 months after prednisolone administration. Opacification of the anterior shallow cortex and the posterior subcapsular layer was observed after 10 months. X-irradiated eyes showed more prominent lens opacification as compared with nonirradiated eyes after 10 months in both group II and group III. Either topical or systemic administrations of prednisolone acetate over a long term successfully induced morphological lenticular changes in the rat similar to those found in human steroid-induced cataracts. A low dose of X-irradiation effectively accelerated opacification as a cocataractogenic risk. This new model will allow future investigation of steroid cataracts.

PURPOSE The goal of this study was to quantify the relationship between the (1) H longitudinal relaxation rate constant, R1 , and oxygen (O2 ) concentration (relaxivity, r1 ) in tissue and to quantify O2 -driven changes in R1 (ΔR1 ) during a breathing gas challenge in normal brain, radiation-induced lesions, and tumor lesions. METHODS R1 data were collected in control-state mice (n = 4) during three different breathing gas (and thus tissue O2 ) conditions. In parallel experiments, pO2 was measured in the thalamus of control-state mice (n = 4) under the same breathing gas conditions using an O2 -sensitive microprobe. The relaxivity of tissue O2 was calculated using the R1 and pO2 data. R1 data were collected in control-state (n = 4) mice, a glioma model (n = 7), and a radiation necrosis model (n = 6) during two breathing gas (thus tissue O2 ) conditions. R1 and ΔR1 were calculated for each cohort. RESULTS O2 r1 in the brain was 9 × 10(-4) ± 3 × 10(-4) mm Hg(-1) · s(-1) at 4.7T. R1 and ΔR1 measurements distinguished radiation necrosis from tumor (P< 0.03 and P< 0.01, respectively). CONCLUSION The relaxivity of O2 in the brain is determined. R1 and ΔR1 measurements differentiate tumor lesions from radiation necrosis lesions in the mouse models. These pathologies are difficult to distinguish by traditional imaging techniques; O2 -driven changes in R1 holds promise in this regard. Magn Reson Med 75:2442-2447, 2016. © 2015 Wiley Periodicals, Inc.

PURPOSE To determine whether the gauge of vitrectomy instrumentation is associated with the progression of nuclear sclerotic cataract. METHODS A prospective interventional and observational study of patients undergoing vitrectomy surgery for various retinal conditions. Patients had Scheimpflug lens photography in the operated and fellow eye at baseline and at 6 months and 12 months after vitrectomy surgery. RESULTS Of 42 eyes included in the analysis, 11 had 20-gauge surgery, 22 had 23-gauge surgery, and 9 had 25-gauge surgery. In all operated eyes, vitrectomy surgery led to the significant progression of nuclear sclerotic cataract, compared with the fellow, unoperated eye. This small study was unable to detect a difference in nuclear sclerotic progression when comparing small-gauge surgery (23 and 25 gauge) with standard 20-gauge surgery. CONCLUSION Removal of the vitreous gel using any-gauge vitrectomy surgery leads to significant progression of nuclear sclerotic cataract at 6 months and 12 months. The findings are consistent with the hypothesis that the vitreous gel is important in protecting the lens from increased exposure to oxygen that leads to the formation of nuclear sclerotic cataract. This increased exposure to oxygen occurs as a result of removing the vitreous gel and is independent of the gauge of vitrectomy instrumentation.

In order to introduce the common marmoset (Callithrix jacchus) into lens research, morphological studies were performed on the anterior eye segment of this monkey. The anterior eye segments of two common marmosets, aged 2 and 5 years, of two cynomolgus monkeys (Macaco fascicularis) with estimated ages of 5 and 10 years and of a 3-year-old child were examined by the EAS-1000 Scheimpflug camera. Scanning electron microscopic observation was performed on the lenses of the monkeys. The biometrical results of the common marmoset, including corneal diameter (4 mm), radial curvature of the cornea (3.5 mm), corneal thickness (0.35 mm), radial curvature of the anterior (9.1 mm) and posterior lens (2.6 mm), whole lens thickness (1.9 mm), equatorial diameter of the lens (5.0 mm) and anterior chamber depth (1.3 mm), were taken from slit images using an equipped EAS-1000 program. Scanning electron microscopic observation of the lens showed no prominent difference between the common marmoset and the cynomolgus monkey. Although some skill was needed to observe the anterior eye segment of the common marmoset without anesthesia, this monkey may be useful for future lens research.

Objective To compare the PO 2 distribution in different regions in the eyes of patients undergoing intraocular surgery. Methods Before initiation of intraocular cataract and/or glaucoma surgery, an optical oxygen sensor was introduced into the anterior chamber via a peripheral corneal paracentesis. The tip of the flexible fiberoptic probe was positioned by the surgeon for 3 measurements in all patients: (1) near the central corneal endothelium, (2) in the mid–anterior chamber, and (3) in the anterior chamber angle. In patients scheduled to undergo cataract extraction, PO 2 was also measured (4) at the anterior lens surface and (5) in the posterior chamber just behind the iris. Oxygen measurements at the 5 locations were compared using a 2-tailed unpaired t test and multivariate regression. Results The PO 2 value was significantly higher in African American patients at all 5 locations compared with Caucasian patients. Adjusting for age increased the significance of this association. Adjusting for race revealed that age was associated with increased PO 2 beneath the central cornea. Conclusions Racial differences in oxygen levels in the human eye reflect an important difference in oxidative metabolism in the cornea and lens and may reflect differences in systemic physiologic function. Increased oxygen or oxygen metabolites may increase oxidative stress, cell damage, intraocular pressure, and the risk of developing glaucoma. Oxygen use by the cornea decreases with age.

Introduction Alterations in intraocular oxygen levels are important contributors to, or indications of, ocular disease. Polarographic electrodes and fibre-optic sensors (optodes) have been used to measure oxygen and to map the distribution of oxygen in animal models and in human eyes. A recent study reported the use of a commercial electrode to compare oxygen distribution in the vitreous of patients undergoing vitrectomy related to central retinal vein occlusion, macular hole or preretinal membrane. The results of this study were at variance with previous measures of oxygen distribution in the human vitreous using polarographic or optical sensors. To resolve this discrepancy, the present study compared measurements made in vitro or in animal eyes, using the electrode employed in the previous study or a fibre-optic sensor of a different design. Study design Comparative in vitro and in vivo measurements. Results In vitro, the two devices reported similar levels of oxygen, although the electrode consistently detected levels above the calculated values. In rabbit eyes, the electrode had a slow response time and was unable to detect oxygen gradients that were readily measured by the smaller optode. When the electrode was inserted into an eye of similar size to the human eye, the reference thermistor measured the temperature outside the eye, not in the vitreous. Conclusions The design of the electrode used in the previous study makes it unsuitable for measurements of oxygen distribution in the eye.

From January 1963 to December 1989, 1585 consecutive cases of retinal detachment were operated with homologous skin as buckling material, the rate of operative success being 91.6%. Human skin is easy to obtain, sterilize and preserve; because of its appropriate thickness and firm but elastic consistency it satisfactorily meets the need to produce sufficient height and to maintain necessary duration of the scleral buckling; in addition to a high rate of reattachment, homologous skin implantation was well tolerated, very rarely rejected (0.06%) and infected (0.25%), and no late complications occurred. Therefore, the authors prefer using human skin as buckling agent rather than conventional synthetic material, e.g., silicon sponge etc.

Publisher Summary Cataract describes any opacification of the lens of the eye. Cataracts can be present at birth (congenital), or develop early in life (juvenile), or in response to ocular trauma. However, the vast majority of cataracts occur in later life. Cataracts are the most common cause of blindness worldwide and cataract surgery is the most frequently performed surgical procedure. Despite aggressive attempts to provide adequate surgical treatment, the worldwide increase in longevity has meant that the number of individuals with impaired sight due to cataract is increasing. Cataracts are often considered to be a natural consequence of the aging process. There are many ways to reduce the risk of cataracts. This chapter evaluates the evidence for several different potential causes of cataracts and highlights the promising approaches for future cataract therapies. Much is known about the development, function and aging of the normal lens. However, developing effective strategies to prevent or slow age-related cataracts will require partnerships between clinicians and basic scientists and the willingness of the ocular pharmaceutical industry to respond to opportunities when they arise.

Cataract and glaucoma are two of the most common ocular morbidities. Previous studies by our group and others have suggested that exposure of the crystalline lens to excessive oxygen may have a critical role in the pathogenesis of age-related nuclear cataracts.1–9 Specifically, the oxygen level is relatively low in the vitreous gel and nuclear cataracts are prone to develop after vitrectomy by increasing lens exposure to oxygen from the posterior segment altering the normally hypoxic environment around the lens. Furthermore, Chang10 reported an increased risk of open angle glaucoma developing after vitrectomy and subsequent cataract surgery. The presence of the natural lens at the time of vitrectomy was associated with a 28-month delay in the onset of glaucoma.10,11 We hypothesized that exposure of the anterior segment to oxygen may increase the risk of glaucoma. A large body of evidence indicates that increased oxidative stress or the accumulation of oxidative damage contributes to the pathogenesis of open angle glaucoma.12–22 Recent studies by our group on oxygen distribution in the human eyes clearly demonstrated that the oxygen level was significantly elevated in aqueous humor near the trabecular meshwork (TM) after combined vitrectomy and cataract surgery. Therefore, it further supports the notion that the elevated oxygen near the TM may contribute to the development of open-angle glaucoma.19–22 Our most recent study also has revealed a steep oxygen gradient in the anterior segment of human eyes with an inverse correlation between central corneal thickness (CCT) and oxygen partial pressure (pO2) exclusively in the anterior chamber (AC) angle.22 As the corneal endothelial pumps require active oxygen consumption, we speculated that corneal endothelial dysfunctions could impact the oxygen tension in the anterior segment of human eyes. This study further explored the oxygen consumption by corneal endothelium and its implications for oxidative stress in the anterior segment. Measurements of pO2 were performed in the anterior segment of patients undergoing either cataract surgery (normal control) or Descemet's stripping automated endothelial keratoplasty (DSAEK) due to Fuchs' endothelial corneal dystrophy (FECD) or pseudophakic bullous keratopathy (PBK).

To report vitreous oxygen tension before, immediately after, and at longer times after vitrectomy.A prospective, interventional consecutive case series.Oxygen was measured using an optical oxygen sensor in patients undergoing vitrectomy. Intraoperatively, oxygen measurements were taken before and after vitrectomy in two intraocular locations: adjacent to the lens and in the mid-vitreous.Sixty-nine eyes underwent oxygen tension measurements at the time of vitrectomy. In baseline eyes, oxygen tension in the vitreous was low, measuring 8.7 +/- 0.6 mm Hg adjacent to the lens and 7.1 +/- 0.5 mm Hg in the mid-vitreous. The difference between the two locations was statistically significant (P.003), indicating that vitreous gel maintains an intraocular oxygen gradient. Immediately after vitrectomy, oxygen tension in the fluid-filled eye was higher, measuring 69.6 +/-4.8 mm Hg adjacent to the lens and 75.6 +/- 4.1 mm Hg in the mid-vitreous. There was no statistically significant oxygen gradient between the two locations. The difference in oxygen tension pre- and postvitrectomy is highly statistically significant (P.0001 lens, P.0001 mid-vitreous). In eyes with a history of vitrectomy and previous removal of the vitreous gel, the intraocular oxygen tension was significantly higher than in eyes with a formed vitreous gel undergoing a first vitrectomy (P.02 lens, P.003 mid-vitreous).Vitrectomy surgery significantly increases intraocular oxygen tension during and for prolonged periods after surgery. This exposes the crystalline lens to abnormally high oxygen and may lead to nuclear cataract formation.

Editor, We read with interest the recent editorial on the physiological effects of vitreous surgery, which highlighted the importance of the viscosity of the vitreous fluid on the rate of diffusion of small molecules of physiological importance (Stefansson & Loftsson 2006). From the Stokes–Einstein equation and previous measurements of the viscosity of the human vitreous body (Lee et al. 1992), it was suggested that the rate of diffusion should be 300–2000 times slower before vitrectomy than after. We agree that the rate at which small molecules are distributed in the eye is an important aspect of ocular physiology. However, the published measures of the viscosity of the vitreous were obtained from vitreous gel, while the Stokes–Einstein equation describes the effect of the viscosity on the rate of diffusion in a liquid. David Maurice measured the rate of loss of radioactive protein from the centre of the vitreous body of living rabbit eyes. Using these measures and physical modelling, he concluded that the rate of diffusion of molecules in the intact vitreous body was experimentally indistinguishable from water (Maurice 1959). Dr Maurice’s measurements have since been used to model the distribution of many kinds of molecules in the eye. To make more direct observations of diffusion in the vitreous body at the microscopic scale, we used fluorescence correlation spectroscopy (FCS) (Elson 2004). FCS measures the time spent by single fluorescent molecules in a tiny volume at the focal point of a laser beam. When their molecular weight is known, FCS provides a measure of the viscosity of the medium in which the molecules are moving. We collected data from the diffusion of two fluorescent molecules of different molecular weight, Alexa 488 (~ 0.5 kDa) and recombinant green fluorescent protein [GFP (~ 29 kDa)], in physiological salt solutions, homogenized porcine vitreous or intact porcine vitreous gel. Correlation spectra were collected using a Zeiss Confocor™ (Thornwood, NY, USA) attachment on a LSM510 confocal microscope (Zeiss Confocor™) at a point 100 μm into the solution or gel. The correlation spectra obtained are shown in Fig. 1; mean diffusion times and calculated diffusion coefficients for Alexa 488 and GFP are shown in Tables 1 and ​and2,2, respectively. Fig. 1 Correlation spectra for Alexa 488 (A) and recombinant green fluorescent protein [GFP (B)] in different media. BSS, balanced salt production; PBS, phosphate-buffered saline. Table 1 Mean diffusion times and calculated diffusion coefficients for Alexa 488. Table 2 Mean diffusion times and calculated diffusion coefficients for recombinant green fluorescent protein (GFP). As expected from its greater molecular weight, GFP had a longer diffusion time and lower diffusion coefficient than Alexa 488 under all conditions. However, the diffusion times and calculated diffusion coefficients of each fluorescent molecule measured in saline solutions, homogenized vitreous or vitreous gel were similar. According to the Stokes–Einstein equation, if the microscopic viscosity of the vitreous fluid or the vitreous gel were greater than saline, the calculated diffusion coefficients in the vitreous fluids would have been proportionally smaller in vitreous (gel or liquid) than in saline. Since these values were similar, the microscopic viscosity of liquid or gel vitreous is similar to saline. These measurements and the work of Dr Maurice suggest that the rate of diffusion of a molecule in the vitreous chamber is expected to be similar before and after vitrectomy and in eyes with an intact vitreous body or with extensive vitreous liquefaction. It has been argued that the loss of the gel structure of the vitreous body, as a consequence of vitrectomy or age-related liquefaction, has important effects on the distribution of small molecules in the eye (Stefansson et al. 1990; Harocopos et al. 2004; Stefansson 2006). The available evidence suggests that the increased rate at which molecules are redistributed in the vitreous compartment in the absence of the vitreous gel or after vitreous degeneration is more likely to be because of an increase in fluid circulation than a difference in the rate of diffusion.

To clarify the histopath ological changes of experimentally induced steroid cataract in Brown-Norway rat eyes, a scanning electron microscopic study was performed. The biomicroscopic appearance of the cataracts, which was quite similar to that of human eyes, was induced by daily application, either topically or systemically, of prednisolone acetate for 12 months. A single dose of 2 Gy X ray was given to the right eyes of all the animals 2 weeks before drug administration. Twenty-seven rats were divided into three groups: a control group (CTL), a group receiving topically administered prednisolone (TOP), and a group receiving systemically administered prednisolone (SYS). In vivo observation was performed through a slit-lamp microscope, and the lens findings were documented and objectively analyzed by an anterior eye segment analysis system over a period of 12 months. At the end of the 12month period, X-ray-irradiated right eyes in the CTL group showed some minor lens changes on biomicroscopy, and non-X-ray-irradiated left eyes were almost normal. In the TOP and SYS groups, either with or without X-ray irradiation, lenses showed anterior and posterior subcapsular opacification; however, the grade and increase of lens opacification were higher and faster in the eyes with X-ray irradiation. Scanning electron microscopic findings of the three groups at the 12th month were as follows. In the CTL group, the X-ray-irradiated right eyes showed minor changes. In the TOP group, the X-rayirradiated right eyes showed marked damage in the lens fibers of the anterior and posterior cortices, while the nonirradiated left eyes showed minor changes. In the SYS group, the X-ray-irradiated right eyes showed prominent cataractous disorganization of lens fibers in the shallow anterior and posterior cortices, and the non-X-ray-irradiated lenses were almost the same as those in the TOP group. These findings might suggest that even a minimum invasion of a low dose of X-ray irradiation plays a cocataractogenic or syncataractogenic role during the formation of steroid cataracts.

The efficacy of a vitamin-E (VE) ophthalmic solution was evaluated on a newly developed rat steroid-induced cataract model. Brown Norway rats irradiated with 2 Gy X-ray, right eyes only, were divided into 5 groups: the control group; 2 steroid (1 mg/kg/day)-treated groups with topic (Top) and systemic (Sys) administration, and 2 VE-treated groups, 1 with the same treatment as the Top group with the addition of 5% VE twice a day (Top + VE) and 1 with the same treatment as the Sys group with 5% VE twice a day (SYS + VE). The lens changes were documented with a Scheimpflug camera and changes in light scattering were evaluated quantitatively. The VE-treated groups (Top + VE and Sys + VE) showed a significant inhibition of the increase in the opaque area compared with each of the non-VE-treated groups. The VE ophthalmic solution was strong enough to prevent steroid-induced cataract in rats.

Several lines of evidence suggest that increased oxidative stress or the accumulation of oxidative damage contributes to the pathogenesis of glaucoma.1–7 Antioxidant protective mechanisms are decreased, and enzymes induced by oxidative stress are increased in the aqueous humor of glaucoma patients, compared with those undergoing cataract surgery.3,8 Oxidative damage to DNA increases in the trabecular meshwork cells of glaucoma patients, and these cells are more susceptible to oxidative DNA damage than are other cells in the anterior segment.9 In one study, the lymphocytes of glaucoma patients had pathogenic mutations in their mitochondrial DNA that were not present in control subjects.10 These alterations are consistent with oxidative damage. The mitochondria of glaucoma patients also had significantly lower oxidative activity than in control subjects.10 Despite the abundant evidence linking glaucoma's pathogenesis to oxidative damage, the source of the oxidative stress in these patients is not known. It is also not clear whether the increased oxidative damage in glaucoma patients is the result of increased exposure to oxidants, decreased antioxidative protection, or a combination of these factors. Ocular surgery can increase the risk of developing glaucoma. Elevated intraocular pressure and glaucoma have long been associated with corneal transplantation (penetrating keratoplasty) or the implantation of an artificial cornea.11–19 Recently, two studies reported that vitrectomy is also associated with increased risk of elevated intraocular pressure and glaucoma. In both studies, the presence of the natural lens delayed the onset of glaucoma.20,21 In most older patients who undergo vitrectomy, nuclear sclerotic cataracts develop within 2 years.22–26 Nuclear cataract is associated with increased oxidative damage to the lens, and vitrectomy leads to increased exposure of the lens to oxygen.23,27,28 These observations led Chang20 to propose that, after vitrectomy, metabolites of oxygen, like hydrogen peroxide, may damage the tissues of the outflow pathway, contributing to the increased risk of glaucoma. Since the presence of the natural lens reduces the risk of glaucoma, he proposed that the lens protects the anterior segment from oxygen or oxygen metabolites. The present study was designed to test Chang's hypothesis that oxygen is relatively low in the anterior segment of the non–surgically altered eye and that it increases after vitrectomy and cataract surgery. The distribution of oxygen in the anterior segment of the eye was measured in a reference group of patients who were undergoing surgery for glaucoma or cataract. Oxygen distribution in these patients was compared with that in patients who had had vitrectomy, cataract surgery, or both procedures. The results of these measurements supported the predictions of the Chang hypothesis, which suggest that increased exposure to oxygen or its metabolites causes open-angle glaucoma. These studies also revealed an unexpected physiologic mechanism that regulates the distribution of oxygen in the anterior chamber angle of the human eye.

To determine whether diabetes mellitus is protective for nuclear sclerotic cataract at baseline and 6 and 12 months after vitrectomy surgery.Prospective, interventional cohort study.Phakic diabetic and nondiabetic patients undergoing vitrectomy surgery for a variety of retinal conditions underwent Scheimpflug lens photography in the operated and fellow eye at baseline and at 6 and 12 months after vitrectomy surgery.Of 52 eyes included in the analysis, 23 eyes were from diabetic patients, 14 of which had surgery for ischemic retinopathy. At baseline, eyes with ischemic diabetic retinopathy had less nuclear sclerotic cataract than nonischemic diabetic and nondiabetic eyes. This was true for eyes undergoing vitrectomy surgery (P = .0001) and for fellow eyes (P = .003). Nuclear sclerotic cataract developed after vitrectomy surgery in nonischemic diabetic eyes and nondiabetic eyes at the same rate. Diabetic eyes with ischemic retinopathy showed no significant progression of nuclear opacification, and therefore had significantly less postvitrectomy nuclear cataract at 6 months (P1 × 10(-6)) and at 12 months (P.001) than nondiabetic or nonischemic diabetic eyes. Normalizing to baseline opacity and adjusting for age and other comorbidities did not alter this result.Ischemic diabetic retinopathy, not just systemic diabetes mellitus, protected against nuclear sclerotic cataract at baseline and after vitrectomy surgery. These findings are consistent with the hypothesis that increased exposure to oxygen is responsible for nuclear cataract formation.

PURPOSE. Vitrectomy is associated with the rapid progression of nuclear cataracts. This study was conducted to test the hypothesis that age-related liquefaction of the vitreous gel may also be associated with lens opacification. METHODS. Lenses from eye bank eyes were graded for nuclear, cortical, and posterior subcapsular opacities, and the amount of liquid vitreous was measured. RESULTS. Nuclear sclerosis (NS) grade, percent liquefaction, and age all correlated highly (P 0.0001). After adjustment was made for age, the correlation between NS and percent liquefaction was 0.37 (P 0.0001), and the correlation between age and NS after adjustment for liquefaction was 0.57 (P 0.0001). After the eyes were stratified into age groups, the correlation between NS and percent liquefaction was found to be highest in eyes from donors aged 51 to 70. Cortical and posterior subcapsular opacities increased with age, but scores for these cataract types did not significantly correlate with vitreous liquefaction. CONCLUSIONS. Loss of vitreous gel during aging increases the risk of nuclear cataracts. Preservation or replacement of the vitreous gel may protect patients from nuclear cataract. (Invest Ophthalmol Vis Sci. 2004;45:77‐ 85) DOI:10.1167/iovs.030820