Monocyte chemoattractant protein-1 in the aqueous humour of patients with age-related macular degeneration

Background: To investigate the role of inflammation in age‐related macular degeneration by measuring the levels of cytokines in the aqueous humour. Methods: Samples of aqueous humour were collected from 34 patients with age‐related macular degeneration and 16 age‐matched control subjects undergoing cataract surgery. Age‐related macular degeneration stage was determined clinically, before surgery. Levels of cytokines were measured using Luminex X‐MAP technology, and positive results were verified by Western blot. Results: Age‐related macular degeneration was moderate in 18 patients and advanced in 16. The advanced age‐related macular degeneration group was further divided into patients with active choroidal neovascularization (n = 7), disciform scar (n = 7) or central geographic atrophy (n = 2). Higher‐than‐normal levels of monocyte chemoattractant protein‐1 in the aqueous humour were associated with advanced age‐related macular degeneration (200 ± 140 pg/mL vs. 100 ± 61 pg/mL; P = 0.03), especially active choroidal neovascularization (255 ± 155 pg/mL; P = 0.02), Western blot analysis verified the monocyte chemoattractant protein‐1 findings. Patients with disciform scar showed a trend of abnormally high levels of interleukin‐12 (p70) (1.7 ± 2.4 pg/mL vs. 0.2 ± 1 pg/mL; P = 0.07), tumour necrosis factor‐α (1.8 ± 2.4 pg/mL vs. 0.3 ± 1 pg/mL; P = 0.06) and interleukin‐12 (4.7 ± 6.4 pg/mL vs. 1.2 ± 2.1 pg/mL; P = 0.08). Conclusion: Elevated levels of inflammation‐related cytokines in the aqueous humour in various stages of age‐related macular degeneration may suggest a pathogenic role of inflammation. Monocyte chemoattractant protein‐1 may be indicative of the angiogenic phase. Further corroborative studies are required.     

Neuroprotective effect of epigallocatechin‐3‐gallate against N‐methyl‐D‐aspartate‐induced excitotoxicity in the adult rat retina

Purpose: Epigallocatechin‐3‐gallate (EGCG), the major polyphenol of green tea, has been suggested to reduce glutamate excitotoxicity. We therefore investigated the potentially protective effects of EGCG against N‐methyl‐d ‐aspartate (NMDA)‐induced excitotoxicity in the retina. Methods: Female Wistar rats (n = 171) were divided into a normal control group (n = 9); saline control group with intravitreal saline injections (n = 54); NMDA control group with an intravitreal NMDA injection and intraperitoneal saline injections (n = 54); and NMDA study group (n = 54) receiving an intravitreal NMDA injection plus intraperitoneal EGCG (25 mg/kg) injections. Starting at 2 days prior to the intravitreal NMDA injection, the intraperitoneal injections were performed daily for the whole study period. At 12 hr, 1, 2, 3 days, 1 and 2 weeks after the intravitreal NMDA injection, the animals were killed. We counted the neurons in the retinal ganglion cell layer (GCL) on histological sections, measured the thickness of Thy‐1 immunoreactivity and assessed the expression of Thy‐1 mRNA by real‐time polymerase chain reaction. Results: At all time‐points, GCL cell density, thickness of Thy‐1 immunoreactivity and expression of Thy‐1 mRNA were significantly (all p < 0.05) lower in the NMDA control group than in the NMDA study group, in which the parameters were significantly (all p < 0.05) lower than in the saline control group and the normal control group. In both groups with an intravitreal NMDA injection, GCL cell density, thickness of Thy‐1 immunoreactivity and expression of Thy‐1 mRNA decreased significantly with increasing follow‐up time. Conclusions: Intraperitoneal application of EGCG resulted in a significantly less marked NMDA‐associated loss of retinal ganglion cells.     

Short exposure to telestereoscope affects the oculomotor system

Under natural viewing conditions, the accommodation and vergence systems adjust the focus and the binocular alignment of the eyes in response to changes in viewing distance. The two responses are linked via cross‐coupling and proceed almost simultaneously. Some optical devices, such as virtual reality or helmet mounted displays, create an oculomotor conflict by modifying demands on both vergence and accommodation. Previous studies extensively investigated the effect of such a conflict on the cross‐coupling between vergence and accommodation, but little is known about the plasticity of the whole oculomotor system. In the present study, an oculomotor conflict was induced by a telestereoscope which magnified the standard inter‐pupillary separation threefold and thus increased the convergence demand while accommodation remained almost unchanged. The effect of a 10 min exposure was assessed via a series of optometric parameters selected on the basis of existing oculomotor models. Associated with subject’s visual complaints, most of the oculomotor parameters tested were modified: there was (1) deterioration of stereoscopic threshold; (2) increase in AC/A ratio; (3) increase in near and far phorias; and (4) shift of the zone of clear and single binocular vision towards convergence. These results showed a change in gain of accommodative vergence and a shift of vergence reserves towards convergence in response to telestereoscopic viewing. The subject’s binocular behaviour tended towards esophoria with convergence excess as confirmed by Sheard’s and Percival’s criteria. Such changes in oculomotor parameters support adaptive behaviour linked with telestereoscopic viewing.     

SARS‐CoV‐2 and COVID‐19 for the ophthalmologist

The COVID‐19 pandemic has had an unprecedented impact on ophthalmology. This review compiles general aspects of the novel coronavirus and COVID‐19, further dissects the most recent data on the role of the eye regarding disease transmission and manifestations, and summarizes preventive measures in the particular context of eye care.     

Dry‐eye syndrome after allogeneic stem‐cell transplantation in children

Purpose: To report the prevalence of dry‐eye syndrome (DES) in children and young adults treated with allogeneic stem‐cell transplantation (SCT) during childhood; to relate DES to conditioning regimes, including total body irradiation (TBI) and chemotherapy, and to immunosuppressive drugs and graft‐versus‐host disease (GVHD). Methods: This cross‐sectional study included 60 children/young adults transplanted because of leukaemia, various haematological disorders and inborn errors of metabolism between 1986 and 2004, with a follow‐up time of 7.0 years (median, range 2–18). Clinical assessments, performed at a median age of 15.6 years (range 5.5–23.5), included an inquiry form on dry‐eye symptoms, corneal status including fluorescein staining, ‘break‐up time’ (BUT) and Schirmer test. Results: A total of 37 of 60 patients had DES defined as presence of corneal epithelial lesions with a pathological BUT and/or Schirmer test. Twenty‐nine had had staining <1–10% of the corneal surface while eight patients had staining ≥10–25% of the corneal surface. All 37 patients with objective signs of DES, graded and not graded, had significant associations to subjective symptoms of dry eyes including dry eyes, red eyes, ocular irritation, secretion and sensitivity to light. Frequent occasions (above median; n = 7) of high cyclosporine A trough levels above 250 ng/ml were associated significantly with DES (P = 0.002). However, there was no association between DES and conditioning with single‐dose (s‐TBI) or fractionated TBI (f‐TBI), busulfan or other chemotherapy. There were no associations between prolonged corticosteroid treatment or chronic GVHD and DES in the present study. DES was more common in patients with malignant diseases (P = 0.02). Malignant disease increased the risk of DES in girls but not in boys. Increased age at SCT increased the risk for DES in boys but not in girls (P = 0.02). Although severe keratitis occurred in three patients, nobody suffered corneal perforation. Conclusion: DES with epithelial punctata keratopathy was common in children/young adults treated with SCT and more common if the patients were exposed to repeated high trough levels of cyclosporine A; however, DES was not associated with irradiation, corticosteroids or GVHD in the present study. Patients with objective DES also had subjective symptoms of dry eyes, which facilitate diagnosis. Girls with malignant diseases and boys who underwent SCT at later ages seem to demand higher attention and more frequent check‐ups regarding DES. Patients with diagnosed severe DES needed frequent and continuous ophthalmological care to maintain treatment motivation.     

The relaxing effect of perivascular tissue on porcine retinal arterioles in vitro is mimicked by N‐methyl‐D‐aspartate and is blocked by prostaglandin synthesis inhibition

Purpose: Retinal hyperperfusion resulting from disturbances in the regulation of arteriolar tone is involved in the pathophysiology of a variety of retinal diseases. The mechanisms underlying this regulation of tone involve cellular components in both the vascular wall and the perivascular tissue. However, previous in vitro studies of the influence of perivascular retinal tissue on retinal tone regulation have been hampered by the release of an endogenous relaxing factor that renders the arteriole insensitive to vasoconstrictors. The purpose of the present study was to test whether N‐methyl‐D‐aspartate (NMDA) and γ‐amino butyric acid (GABA) receptors, and a cyclooxygenase (COX) product influence this effect of perivascular retinal tissue in vitro. Methods: Porcine retinal arterioles were mounted in a wire myograph for isometric force measurements. The contractile effect of the prostaglandin analogue U46619 was studied on vessels with preserved perivascular retinal tissue and after this tissue had been removed. The influence of the perivascular tissue was studied after addition of NMDA (a specific agonist for a subtype of the glutamate receptor), DL‐amino‐5‐phosphonovaleric acid (DL‐APV, an antagonist at the same receptor), the natural inhibitory transmitter GABA, and picrotoxin (an antagonist at ionotropic GABA receptors). These experiments were made in the absence and presence of the COX inhibitor, ibuprofen. Results: U46619 caused a concentration‐dependent contraction of isolated retinal arterioles. This vasoconstriction was significantly smaller in the presence of perivascular tissue. The NMDA‐receptor antagonist, DL‐APV, reduced this attenuating influence of the perivascular tissue on the response to U46619, and the response could be modified by NMDA and GABA, but not by picrotoxin. However, ibuprofen totally blocked the attenuating influence of the perivascular tissue on the response to U46619. Conclusions: The inhibition of vascular contractility induced by perivascular retinal tissue in vitro involves NMDA‐receptors and an effect of GABA‐mimetic substance on retinal tissue. The generation of these effects involves a COX product.     

Feasibility of multifocal intra‐ocular lens exchange and conversion to the bag‐in‐the‐lens implantation

Purpose: Our purpose was to evaluate the surgical outcome after intra‐ocular lens exchange in patients who presented impairing visual complaints after primary multifocal intra‐ocular lens (MIOL) implantation. In particular, the study was undertaken to look at the number of eyes that could be equipped with the bag‐in‐the‐lens (BIL) IOL after MIOL exchange. Methods: This series consisted of 30 eyes of 21 consecutive patients scheduled for MIOL exchange. In 15 out of the 30 eyes, IOL misalignment was measured on slit lamp anterior segment photo’s after defining the mathematical centres of the IOL optic, pupil and limbus. Results: Diffractive MIOL was more frequently explanted (25; 83%) when compared with refractive MIOL (4; 13%) and progressive optic IOL (1; 4%). In 21 out of the 30 eyes (70%) a bag‐in‐the‐lens could be implanted. In 7 out of the 30 eyes (23%), the capsule was not considered sufficiently stable to accommodate an IOL. An iris‐fixated IOL or a sulcus‐fixated IOL was then implanted. In 2 out of the 30 eyes (6%) the remaining capsular bag could accommodate a traditional lens‐in‐the‐bag only. Eyes that underwent Nd:YAG laser capsulotomy prior to the MIOL exchange needed anterior vitrectomy peroperatively (11 eyes; 37%). Visual acuity improved postoperatively in 13 out of the 30 eyes and remained stable in 17 out of the 30 eyes. Conclusions: Since the BIL technique requires a very well‐preserved capsular bag for the purpose of the IOL implantation, the success rate of BIL implantation after MIOL is a good indicator to evaluate the degree of difficulty to exchange MIOL.     

Peripheral autofluorescence findings in age‐related macular degeneration

Purpose: To describe the peripheral autofluorescent findings in patients with age‐related macular degeneration (AMD) using ultrawide‐field imaging. Methods: We retrospectively reviewed the ultra‐wide‐field autofluorescent images of all patients diagnosed with AMD or macular drusen at the Department of Ophthalmology of Weill Cornell Medical College from July 2010 to September 2011. Peripheral autofluorescent phenotypes included normal autofluorescence, focal pinpoint hyperfluorescence, granular fluorescent changes, patchy hypofluorescence, and reticular hypofluorescence. Results: One hundred and ten consecutive patients (220 eyes) with a diagnosis of AMD or macular drusen were imaged using ultra‐wide‐field autofluorescent technology during the study period. Eighty‐three patients (157 eyes) were included in the final analysis. Peripheral autofluorescent abnormalities were present in 63.6% of eyes with AMD versus 35.7% of control eyes (p = 0.049). Granular fluorescent changes (p = 0.0001) and patchy hypofluorescence (p = 0.0015) were more common in eyes with advanced AMD than in eyes with early AMD or control eyes. Granular fluorescent changes were also more common in eyes with choroidal neovascularization (p = 0.026) or geographic atrophy (p = 0.0001). Patchy hypofluorescence (0.0001) was more common in eyes with geographic atrophy. Conclusions: Peripheral autofluorescent abnormalities are common in eyes with AMD. The peripheral findings in eyes with AMD may represent different phenotypes, which may indicate different environmental or genetic factors in the development of AMD. Characterizing the different peripheral phenotypes may have implications for diagnosis and treatment of AMD subtypes.     

Excimer laser surface ablation: a review of recent literature

The aim was to review the recently published literature on excimer laser surface ablation procedures, including photorefractive keratectomy (PRK), laser sub‐epithelial keratomileusis (LASEK), microkeratome‐assisted PRK (epi‐LASIK) and trans‐epithelial (laser‐assisted) PRK, to help elucidate where and how surface ablation may best fit into current refractive surgical practice. The emphasis was on publications within the last three years and included systemic reviews, meta‐analyses and randomised controlled trials. Where such evidence did not exist, selective large series cohort studies, case‐controlled studies and case series with follow‐up preferably greater than six months were examined and included. Refractive and visual outcomes are excellent and comparable to those after LASIK even in complex cases after previous corneal surgery. Indeed, surface ablation combined with corneal collagen cross‐linking may be used in selected eyes with biomechanical instability, where LASIK is contraindicated. In addition, there is evidence to suggest that there may be less induction of higher order aberrations with surface techniques. Long‐term stability and safety appear to be extremely satisfactory. The literature supports the use of modern excimer laser surface treatments, with outcomes comparable to those after LASIK and evidence of less induction of higher‐order aberrations. Follow‐up studies at 10 to 20 years indicate excellent stability and safety.     

Vogt-Koyanagi-Harada disease presenting as acute angle closure glaucoma at onset

Background: To investigate the clinical features of Vogt‐Koyanagi‐Harada (VKH) disease presenting as acute angle closure glaucoma at onset. Design: Retrospective non‐comparative case series. Participants: Four hundred and eighty‐six VKH patients seen from February 2001 to March 2010. Methods: The history and clinical findings of all patients were reviewed. Auxiliary examinations, including ultrasound biomicroscopy, fundus fluorescein angiography and optical coherence tomography, were performed in certain cases. Corticosteroids with or without cyclosporine A were used to treat these patients. Main Outcome Measure: Patients' demographics, clinical presentation and auxiliary examination findings. Results: Eight out of 486 VKH patients were misdiagnosed as acute angle closure glaucoma. The mean age of these eight patients was 55.6 years. Six patients were female. The mean intraocular pressure (IOP) at disease onset was 32.9 mmHg. All of these patients had a shallow anterior chamber and a narrow or closed angle at their first visit. The complaints of these patients were mostly headache and sudden decreased vision in both eyes. Alterations shown on ultrasound biomicroscopy included detachment of the ciliary body and peripheral choroid. The increased IOP did not respond to anti‐glaucoma therapy, but resolved following treatment with corticosteroids. The eye of one patient was enucleated after failed trabeculectomies prior to referral to our uveitis centre. Conclusion: VKH disease presenting with a bilateral increased IOP mostly occurs in older women. The strikingly decreased visual acuity associated with mild to moderate increased IOP is a clue to the diagnosis. The increased IOP responded well to corticosteroids but not to anti‐glaucoma treatment.     

Increased serum total antioxidant status and decreased urinary 8‐hydroxy‐2′‐deoxyguanosine levels in patients with normal‐tension glaucoma

Acta Ophthalmol. 2010: 88: e259–e264

Abstract.

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.