Nanosecond laser therapy reverses pathologic and molecular changes in age-related macular degeneration without retinal damage.

Age-related macular degeneration (AMD) is a leading cause of vision loss, characterized by drusen deposits and thickened Bruch's membrane (BM). This study details the capacity of nanosecond laser treatment to reduce drusen and thin BM while maintaining retinal structure. Fifty patients with AMD had a single nanosecond laser treatment session and after 2 yr, change in drusen area was compared with an untreated cohort of patients. The retinal effect of the laser was determined in human and mouse eyes using immunohistochemistry and compared with untreated eyes. In a mouse with thickened BM (ApoEnull), the effect of laser treatment was quantified using electron microscopy and quantitative PCR. In patients with AMD, nanosecond laser treatment reduced drusen load at 2 yr. Retinal structure was not compromised in human and mouse retina after laser treatment, with only a discrete retinal pigment epithelium (RPE) injury, and limited mononuclear cell response observed. BM was thinned in the ApoEnull mouse 3 mo after treatment (ApoEnull treated 683 ± 38 nm, ApoEnull untreated 890 ± 60 nm, C57Bl6J 606 ± 43 nm), with the expression of matrix metalloproteinase-2 and -3 increased (>260%). Nanosecond laser resolved drusen independent of retinal damage and improved BM structure, suggesting this treatment has the potential to reduce AMD progression.

Hypoxia-induced retinal ganglion cell damage through activation of AMPA receptors and the neuroprotective effects of DNQX.

Hypoxia-induced glutamate accumulation in neural tissues results in damage to neurons through excitotoxic mechanisms via activation of glutamate receptors (GluRs). Here we examine whether hypoxia in the developing retina would cause activation of the ionotropic α-amino-3-hydroxy-5-methylisoxazole-4-propioate (AMPA) GluRs and increase in Ca(2+) influx into retinal ganglion cells (RGCs) that might ultimately lead to their death. Neonatal Wistar rats were subjected to hypoxia for 2h and then sacrificed at various time points after the exposure together with normal age matched control rats. Primary cultures of RGCs were also prepared and subjected to hypoxia. Expression of AMPA glutamate receptor (GluR) 1-4 was examined in the retina. Additionally, expression of GluRs, intracellular Ca(2+) influx, reactive oxygen species (ROS) generation and cell death were investigated in cultured RGCs. GluR1-4 mRNA and protein expression showed a significant increase (P < 0.01) over control values after the hypoxic exposure both in vivo and in vitro. Cells expressing GluR1-4 in the retina were identified as RGCs by double immunofluorescence labeling with Thy1.1. Increased intracellular Ca(2+) in cultured RGCs following hypoxic exposure was reduced (P < 0.01) by 10 µM AMPA antagonist 6, 7-dinitroquinoxaline-2,3-dione (DNQX). Our results suggest that following a hypoxic insult, an increased amount of glutamate accumulates in the neonatal retina. This would then activate AMPA receptors which may damage RGCs through increased Ca(2+) accumulation and ROS generation. The involvement of AMPA receptors in damaging the RGCs is evidenced by suppression of intracellular Ca(2+) influx by DNQX which also decreased ROS generation and cell death by 50%.

A role for photoreceptors in retinal oedema and angiogenesis: an additional explanation for laser treatment?

PURPOSE: To investigate the possible roles of retinal photoreceptors in macular oedema and retinal angiogenesis with particular reference to the mode of action of laser therapy. METHODS: (i) Studies in rats made hypoxic for 2 h by administering an oxygen/nitrogen mixture of reduced oxygen content, and growth factors determined by RT-PCR, western blotting, and immunohistochemistry. Assessment of blood-retinal barrier integrity using fluorescent and electron-dense tracers. (ii) Studies in pigs with one retina made hypoxic by selective embolisation of the retinal capillary circulation with fluorescent microspheres. (iii) Assessment of laser therapy in selected cases of retinal neovascularisation indicating a role for photoreceptors. RESULTS: In the hypoxic retina, angiogenic and vascular permeability factors such as vascular endothelial growth factor (VEGF), nitric oxide synthases (NOSs), and insulin-like growth factor-1 are upregulated in retinal astrocytes and Müller cells but are also present in large amount in the photoreceptors. Hypoxia-inducible factor-1 (HIF-1) is upregulated in retinal glial cells but not in the photoreceptors, suggesting that growth factors in the photoreceptors may not have been generated there. The tracer dye, rhodium isothiocyanate, leaking from an abnormally permeable inner blood-retinal barrier in the hypoxic retina accumulates in the photoreceptors. CONCLUSIONS: The results indicate that laser treatment of macular oedema or retinal neovascularisation may obtain its effect not only by improving oxygen availability in the inner retina, but also by reducing the load of angiogenic/permeability factors that accumulate in the photoreceptors in hypoxic/ischaemic conditions.

Correlation between peripapillary atrophy and corticosteroid therapy in patients with Vogt-Koyanagi-Harada disease.

AIMS: To determine the correlation between systemic corticosteroid therapy and the occurrence and size of peripapillary atrophy (PPA) in patients with Vogt-Koyanagi-Harada (VKH) disease. METHODS: All patients with VKH disease were retrospectively reviewed for their corticosteroid regimen. The extent of the PPA, if present, was measured using digitized imaging software, by two masked observers. Eyes with myopia greater than 6 dioptres or glaucoma were excluded. The patients were classified into three groups: early high (EH), late high (LH), and low dose (LD), according to the dose and timing of corticosteroids received during the acute phase of the disease. RESULTS: There were 40 eyes in the EH group, 25 eyes in the LH group, and 23 eyes in the LD group. Multivariate analysis showed that corticosteroid therapy was the main determinant of PPA occurrence. All the eyes in the LD group had PPA and eyes in the LH groups were 4.02 times (95% confidence interval 1.24-13.07) more likely to develop PPA than those in the EH group. The LD group also had larger PPA to disc ratios than the EH group. (Mean of 2.83 vs0.19, P<0.001). CONCLUSION: The development and extent of PPA in patients with VKH disease appear to be dependent on the dose and timing of systemic corticosteroids.

Factors associated with decompression and strabismus surgery in thyroid eye disease.

INTRODUCTION: Prognostication of the thyroid patient with eye disease aids in the choice of treatment strategy. To facilitate this, we investigated factors associated with decompression and/ or strabismus surgery in the Singaporean population. MATERIALS AND METHODS: A 5-year retrospective study was performed. Patients who required strabismus and/or decompression surgery (n = 23) were compared to those who did not undergo either surgery (n = 44). Individual and multivariate age-adjusted odds ratios were calculated to determine significant associations. RESULTS: Individually, male gender [odds ratio (OR), 4.5; 95% confidence interval (CI), 1.5 to 13.4], uncontrolled hyperthyroidism (OR, 4.0; 95% CI, 1.1 to 14.3), steroid therapy (OR, 7.4; 95% CI, 2.3 to 24), diplopia (OR, 7.3; 95% CI, 2.3 to 23.1), objective vertical myopathy (OR, 11.7; 95% CI, 1.4 to 96.0), elevated intraocular pressure in the primary position (OR, 3.4; 95% CI, 1.2 to 10.0) and clinical evidence of optic neuropathy (OR, 13.1; 95% CI, 1.4 to 124.6) were significantly associated with the need for surgery. Logistic regression analysis showed the greater impact of male gender (OR, 4.2; 95% CI, 1.2 to 15.4), optic neuropathy (OR, 13.0; 95% CI, 1.2 to 143.7) and previous steroid therapy (OR, 4.2; 95%CI, 1.1 to 16.2) on prognostication. CONCLUSIONS: Chances of requiring strabismus and/or decompression surgery are significantly higher for male patients and those with uncontrolled hyperthyroidism. In particular, male patients with optic neuropathy and a history of previous steroid therapy warrant a graver prognosis.

Multifocal electroretinogram in children on atropine treatment for myopia.

AIM: To assess retinal function by multifocal electroretinogram (mfERG) in children on atropine eye drops for the treatment of myopia. METHODS: mfERGs were recorded in children receiving atropine eye drops (n = 48) once daily for 2 years and in those receiving placebo eye drops (n = 57) for a similar time. All recordings were performed between the second and third month of cessation of atropine/placebo treatment by a masked investigator. The amplitude and implicit time of the first order kernel (k1) and first slice of the second order kernel (k21) of mfERG responses were used to study the outer and inner retinal function, respectively. RESULTS: There was no significant reduction in k1 response amplitudes of the atropine group compared to that of the placebo group (N1, p = 0.181; P1, p = 0.150). No significant difference in the k1 response implicit times between the groups was found (N1, p = 0.767; P1, p = 0.849). The differences in the k21 amplitudes and implicit times between the groups were not statistically significant (k21 amplitude, p = 0.058; k21 implicit time, p = 0.156). CONCLUSIONS: Daily atropine usage over 2 years for the treatment of myopia has no significant effect on retinal function as demonstrated by recordings of mfERG.

Effects of a non-steroidal (ketorolac tromethamine) and a steroidal (dexamethasone) anti-inflammatory drug on refractive state and ocular growth.

Topical steroidal anti-inflammatory drugs (SAID) and non-steroidal anti-inflammatory drugs (NSAID) are known to affect fluid balance. The effects of twice daily topical applications of Maxidex (dexamethasone, a SAID), Acular (ketorolac, a NSAID), and saline were examined biometrically on the development of refractive errors and eye growth in chicks raised from days 3-12 wearing either a monocular +10 D, 0 D, or -10 D lens. Biometric analysis showed that neither SAID nor NSAID nor saline affected refractive error compensation but that the anti-inflammatory drugs affected eye growth. In chicks reared with a +10 D lens, dexamethasone induced a decrease in axial length (AL), vitreous chamber (VC) and anterior chamber (AC) depth, while ketorolac only induced a decrease in AC. In -10 D lens chicks dexamethasone again induced a decrease in AL and VC, but did not affect AC depth, whereas ketorolac only induced an increase in AC depth. Taken together, these results suggest that anti-inflammatory drugs can induce changes in ocular size without affecting refractive state and, as such, have implications for the management of progressive myopia.

Vertical fixation disparity curve and the effects of vergence training in a normal young adult population.

BACKGROUND: The vertical forced vergence fixation disparity (VFD) curve represents the amount of vertical fixation disparity, the steady-state vertical bifixation error of the eyes, at various levels of vertical vergence demand. The main aim of the present study was to examine the effects of vertical vergence training on the slope of the VFD curve in a normal, young adult population. METHODS: Forty-five subjects with normal vision and binocular function underwent vertical vergence training for 1 week. The training was done using a vertical prism bar, and the vertical fixation disparity was measured using the Disparometer. RESULTS: The mean slope of the VFD curve in a normal, young adult population was 1.103 min arc/delta. The slope of the VFD curve decreased significantly after the training and remained flattened for at least 3 months. There was no evidence to support the idea that the decrease in the VFD slope was related to the increase of vertical fusional amplitude. CONCLUSIONS: Vertical prism bar training provided a long-term effect, both increasing the vertical fusional amplitude and flattening the slope of the VFD curve. The decrease in the slope of the VFD curve was thought to be independent of the increase of vertical fusional amplitude.

Pterygium surgery in Victoria: a survey of ophthalmologists.

AIM: To determine the surgical approaches and adjunctive therapy es currently used by Victorian ophthalmologists for the treatment of primary and recurrent pterygia. METHOD: Ophthalmologists practising in Victoria were asked to complete a written survey relating to their experience with pterygium surgery. RESULTS: Responses were received from 142 of 165 ophthalmologists surveyed (86%). Of these, 107 (75%) had performed at least one pterygium operation during the preceding 2 years. Excision followed by beta irradiation was the most commonly performed procedure for both primary (57%) and recurrent (35%) pterygia. The next most commonly performed procedure for primary pterygia was excision leaving bare sclera (15%) and, for recurrent pterygia, excision with autologous conjunctival transplantation (26%). Considerable variation was observed in surgical technique, choice of adjunctive therapy, postoperative care and in the surgeons' estimates of the frequency of major complications. CONCLUSION: Although there is little consensus regarding the surgical management of pterygium, beta irradiation remains the most commonly used adjunctive therapy in Victoria.