South Australian Institute of Ophthalmology

Adelaide, Australia

South Australian Institute of Ophthalmology

Adelaide, Australia
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Chidlow G.,South Australian Institute of Ophthalmology | Chidlow G.,University of Adelaide | Wood J.P.M.,South Australian Institute of Ophthalmology | Wood J.P.M.,University of Adelaide | And 4 more authors.
Neurobiology of Disease | Year: 2012

It is increasingly recognised that chronically activated glia contribute to the pathology of various neurodegenerative diseases, including glaucoma. One means by which this can occur is through the release of neurotoxic, proinflammatory factors. In the current study, we therefore investigated the spatio-temporal patterns of expression of three such cytokines, IL-1β, TNFα and IL-6, in a validated rat model of experimental glaucoma.First, only weak evidence was found for increased expression of IL-1β and TNFα following induction of ocular hypertension. Second, and much more striking, was that robust evidence was uncovered showing IL-6 to be synthesised by injured retinal ganglion cells following elevation of intraocular pressure and transported in an orthograde fashion along the nerve, accumulating at sites of axonal disruption in the optic nerve head. Verification that IL-6 represents a novel marker of disrupted axonal transport in this model was obtained by performing double labelling immunofluorescence with recognised markers of fast axonal transport. The stimulus for IL-6 synthesis and axonal transport during experimental glaucoma arose from axonal injury rather than ocular hypertension, as the response was identical after optic nerve crush and bilateral occlusion of the carotid arteries, each of which is independent of elevated intraocular pressure. Moreover, the response of IL-6 was not a generalised feature of the gp130 family of cytokines, as it was not mimicked by another family member, ciliary neurotrophic factor. Finally, further study suggested that IL-6 may be an early part of the endogenous regenerative response as the cytokine colocalised with growth-associated membrane phosphoprotein-43 in some putative regenerating axons, and potently stimulated neuritogenesis in retinal ganglion cells in culture, an effect that was additive to that of ciliary neurotrophic factor. These data comprise clear evidence that IL-6 is actively involved in the attempt of injured retinal ganglion cells to regenerate their axons. © 2012 Elsevier Inc.

Chidlow G.,South Australian Institute of Ophthalmology | Chidlow G.,University of Adelaide | Ebneter A.,South Australian Institute of Ophthalmology | Ebneter A.,University of Adelaide | And 4 more authors.
Acta Neuropathologica | Year: 2011

The neurodegenerative disease glaucoma is characterised by the progressive death of retinal ganglion cells (RGCs) and structural damage to the optic nerve (ON). New insights have been gained into the pathogenesis of glaucoma through the use of rodent models; however, a coherent picture of the early pathology remains elusive. Here, we use a validated, experimentally induced rat glaucoma model to address fundamental issues relating to the spatio-temporal pattern of RGC injury. The earliest indication of RGC damage was accumulation of proteins, transported by orthograde fast axonal transport within axons in the optic nerve head (ONH), which occurred as soon as 8 h after induction of glaucoma and was maximal by 24 h. Axonal cytoskeletal abnormalities were first observed in the ONH at 24 h. In contrast to the ONH, no axonal cytoskeletal damage was detected in the entire myelinated ON and tract until 3 days, with progressively greater damage at later time points. Likewise, down-regulation of RGC-specific mRNAs, which are sensitive indicators of RGC viability, occurred subsequent to axonal changes at the ONH and later than in retinas subjected to NMDA-induced somatic excitotoxicity. After 1 week, surviving, but injured, RGCs had initiated a regenerative-like response, as delineated by Gap43 immunolabelling, in a response similar to that seen after ON crush. The data presented here provide robust support for the hypothesis that the ONH is the pivotal site of RGC injury following moderate elevation of IOP, with the resulting anterograde degeneration of axons and retrograde injury and death of somas. © 2011 The Author(s).

Gupta A.,South Australian Institute of Ophthalmology | Muecke J.,South Australian Institute of Ophthalmology | Muecke J.,University of Adelaide
British Journal of Ophthalmology | Year: 2010

Aim: To report the outcome of treatment of non-invasive ocular surface squamous neoplasia (or conjunctival-corneal intra-epithelial neoplasia (CCIN)) where topical mitomycin C (MMC) has been used in the treatment regimen. Design: Prospective, non-comparative interventional case series. Participants: 91 primary or recurrent CCIN lesions from 90 patients treated in a single ocular oncology centre over a 10.5-year period. Intervention: 73 cases of localised, non-invasive CCIN and eight cases of recurrent CCIN received a treatment regimen of surgical excision±cryotherapy, followed by two to three 1-week cycles of adjuvant topical MMC (0.04% four times a day). 10 cases of diffuse CCIN received two to three 1-week cycles of topical MMC (0.04% four times a day) as sole primary treatment. Main outcome measure: Successful treatment was defined as no clinical recurrence of CCIN. Results: Mean follow-up of 56.8 months (range 5.8 to 119.8) and median 57.3 months, revealed no recurrences (0%) in the localised primary group, and one persistent case and two recurrences (30%) in the diffuse primary group. There was one recurrence (12.5%) in the recurrent group, but this was in the only eye with a diffuse type of recurrence. Conclusions: MMC treatment following surgical excision appears to decrease the recurrence rate of localised CCIN and should be considered as adjuvant therapy in primary treatment. MMC should also be considered as adjuvant therapy in the treatment of localised recurrent disease. MMC may be used as sole therapy in more diffuse disease, but close ongoing follow-up is recommended in view of the significant risk of persistent or recurrent disease.

Rudkin A.K.,South Australian Institute of Ophthalmology | Rudkin A.K.,University of Adelaide | Dempster L.,South Australian Institute of Ophthalmology | Muecke J.S.,South Australian Institute of Ophthalmology | Muecke J.S.,University of Adelaide
Clinical and Experimental Ophthalmology | Year: 2015

Background: Ocular surface squamous neoplasia (OSSN) characterized by diffuse conjunctival or corneal spread is much less common than localized conjunctival disease. However, it is an important subcategory of the disease because of the difficulty it poses to treatment. It is rarely amenable to simple excision, and a purely surgical approach usually necessitates ocular surface reconstruction. Primary treatment with topical chemotherapy is an alternative, but its efficacy for these lesions is not well understood. Design: Retrospective case series. Participants: Thirty-eight eyes treated for diffuse OSSN, defined as a lesion extending over five or more limbal clock hours or by extensive central or paracentral corneal spread. Methods: Treatment utilized either topical 5-FU 1% or mitomycin-C (MMC) 0.04%. Main Outcome Measures: (i) Disease remission; (ii) complications. Results: Thirty-two patients were treated for a primary diffuse OSSN. Ten patients (31%) required further treatment for disease persistence or recurrence. Thirteen patients had previously undergone a single unsuccessful treatment course for diffuse OSSN. Administration of a second treatment course (whether MMC or 5FU) was successful in 46% (six) of patients. 5-FU 1% resulted in drug-related complications in seven of 12 cases, and included a single case of focal paracentral corneal stromal melt. MMC 0.04% resulted in transient drug related complications in 23 of 39 cases. Conclusion: Diffuse OSSN is often recalcitrant to initial treatment with either 5-FU 1% or MMC 0.04%, and a pragmatic and vigilant approach to this heterogenous disease is required. Compared to localized disease, diffuse disease often requires multiple treatment efforts. © 2014 Royal Australian and New Zealand College of Ophthalmologists.

Bahrami B.,South Australian Institute of Ophthalmology | Bahrami B.,University of Adelaide | Greenwell T.,South Australian Institute of Ophthalmology | Greenwell T.,University of Adelaide | And 2 more authors.
Clinical and Experimental Ophthalmology | Year: 2014

Background: To report rates of recurrence and complications of localized ocular surface squamous neoplasia treated with 5-fluorouracil or mitomycin C as adjunctive treatment to surgical excision. Design: Long-term follow up of two prospective, non-comparative interventional case series. Participants: One hundred fifty-three eyes with histologically confirmed localized, non-invasive ocular surface squamous neoplasia. 89 eyes were treated with adjuvant 5-fluorouracil and 64 eyes were treated with adjuvant mitomycin C. Methods: Following surgical excision±cryotherapy patients received topical 5-fluorouracil 1% four times daily for two weeks or topical mitomycin C 0.04% four times daily for two to three 1-week cycles. Main Outcome Measures: Ocular surface squamous neoplasia recurrence, complications of therapy and compliance. Results: Median follow up was 33.6 (range 12-84) months and 57.9 (range 12-160) months in 5-fluorouracil and mitomycin C groups, respectively. There was one recurrence in the 5-fluorouracil group and no recurrences in the mitomycin C group. Side-effects occurred in 69% of 5-fluorouracil patients and 41% of mitomycin C patients. Five patients (6%) required intervention for treatment-related side-effects in the 5-fluorouracil group versus 11 (17%) in the mitomycin C group. No vision-threatening complications were noted. Conclusions: Long-term recurrence of localised ocular surface squamous neoplasia is rare when topical 5-fluorouracil or mitomycin C are used as adjunctive treatment to surgical excision. While side-effects are common, the majority are transient and rarely limit compliance. © 2013 Royal Australian and New Zealand College of Ophthalmologists.

Chidlow G.,South Australian Institute of Ophthalmology | Shibeeb O.,South Australian Institute of Ophthalmology | Shibeeb O.,University of Adelaide | Plunkett M.,Ellex R and D Pty Ltd | And 3 more authors.
Investigative Ophthalmology and Visual Science | Year: 2013

PURPOSE. Retinal laser photocoagulation represents a major treatment strategy for the management of diabetic macular edema (DME). However, the thermal nature of this procedure defines that collateral tissue injury result, meaning that it cannot be used near the fovea centralis. We studied inflammatory and glial responses resulting from treatment of rats with a conventional laser and with a novel short-duration, nonthermal laser (retinal regeneration therapy [2RT]) at clinically relevant energy levels. METHODS. Pigmented Dark Agouti rats were treated with either a conventional thermal continuous wave (CW; 532-nm, 100-ms pulse duration) or a short-pulse (2RT; 532-nm, Q-switched, 3- ns pulse) laser. Settings were at visible threshold for the CW laser (12.7 J/cm2/pulse) and at supra- and subvisible thresholds for the 2RT laser ("high," 2RT-H, 163 mJ/cm2/pulse; "low," 2RT-L, 109 mJ/cm2/pulse). Rats were killed at various subsequent time points. Samples were processed for histology, immunohistochemistry, RT-PCR, and Western blotting. RESULTS. The CW laser caused outer retinal lesions that were associated with photoreceptor death, astrocyte and M̈uller cell activation, and infiltration of macrophages and neutrophils. Furthermore, inflammatory cytokines, heat shock proteins, endogenous trophic factors, and matrix metalloproteinases were induced. In comparison, all of these changes were drastically attenuated when the 2RT laser was used, particularly at the subthreshold setting. CONCLUSIONS. The conventional laser produced marked retinal damage and cellular responses consistent with an inflammatory response to thermal injury. In contrast, the 2RT laser produced negligible retinal damage and cellular responses at clinically relevant settings. These results may have important implications for the treatment of retinal disease. © 2013 The Association for Research in Vision and Ophthalmology, Inc.

Wood J.P.M.,South Australian Institute of Ophthalmology | Wood J.P.M.,University of Adelaide | Shibeeb O.,University of Adelaide | Plunkett M.,Ellex R and D Pty. Ltd. | And 4 more authors.
Investigative Ophthalmology and Visual Science | Year: 2013

PURPOSE. To determine detailed effects to retinal cells and, in particular, neurons following laser photocoagulation using a conventional 532 nm Nd:YAG continuous wave (CW) laser. Furthermore, to determine whether a novel 3 ns pulse laser (retinal regeneration therapy; 2RT) could specifically ablate retinal pigment epithelium (RPE) cells without causing collateral damage to other retinal cells. METHODS. Adult Dark Agouti (DA) rats were separated into four groups: control, CW laser (12.7 J/cm2/pulse, 100 ms pulse duration), or 3 ns pulse 2RT laser at one of two energy settings ("High," 2RT-H, 163 mJ/cm2/pulse; "Low," 2RT-L, 109 mJ/cm2/ pulse). Animals were treated and killed after 6 hours to 7 days, and retina/RPE was analyzed by histologic assessment, Western blot, polymerase chain reaction, and immunohistochemistry. RESULTS. Both lasers caused focal loss of RPE cells with no destruction of Bruch's membrane; RPE cells were present at lesion sites again within 7 days of treatments. CW and 2RT-H treatments caused extensive and moderate damage, respectively, to the outer retina. There were no obvious effects to horizontal, amacrine, or ganglion cells, as defined by immunolabeling, but an activation of PKCα within bipolar cells was noted. There was little discernible damage to any cells other than the RPE with the 2RT-L treatment. CONCLUSIONS. Conventional laser photocoagulation caused death of RPE cells with associated widespread damage to the outer retina but little influence on the inner retina. The novel 3 ns 2RT laser, however, was able to selectively kill RPE cells without causing collateral damage to photoreceptors. Potential benefits of this laser for clinical treatment of diabetic macular edema are discussed. © 2013 The Association for Research in Vision and Ophthalmology, Inc.

Ebneter A.,South Australian Institute of Ophthalmology | Ebneter A.,University of Adelaide | Casson R.J.,South Australian Institute of Ophthalmology | Casson R.J.,University of Adelaide | And 4 more authors.
Investigative Ophthalmology and Visual Science | Year: 2010

PURPOSE. Glia are the main cellular CNS elements initiating defense mechanisms against destructive influences and promoting regenerative processes. The aim of the current work was to characterize the microglial response within the visual pathway in a rat model of experimental glaucoma and to correlate the microglial response with the severity of axonal degeneration. METHODS. Experimental glaucoma was induced in each right eye of adult Sprague-Dawley rats by translimbal laser photocoagulation of the trabecular meshwork. Rats were subsequently killed at various times from 3 days to 6 weeks. Tissue sections were obtained from globes, optic nerves, chiasmata, and optic tracts for immunohistochemistry and toluidine blue staining. RESULTS. This model of experimental glaucoma led to a marked activation of microglia in the retina, optic nerve, and tract. Indeed, microglial activity remained elevated, even after intraocular pressure returned to basal levels. It is postulated that this process accompanies ongoing axonal degeneration. The degree of activation in the optic nerve correlated with axonal damage. Activation was characterized by increased density and morphologic changes. Both major histocompatibility complex (MHC) class I and MHC class II surface proteins were persistently upregulated in optic nerves and localized to microglial cells; however, this did not correlate with any significant T-cell infiltration. Interestingly, MHC class II expression was not detected in the retina. CONCLUSIONS. The present data may have implications for the study of the pathology associated with the visual pathway in diseases such as glaucoma. © Association for Research in Vision and Ophthalmology.

Marcet M.M.,University of Hong Kong | Marcet M.M.,University of Chicago | Meyer D.R.,Lions Eye Institute | Greenwald M.J.,University of Chicago | And 2 more authors.
Ophthalmology | Year: 2013

Purpose: To examine the tarsal attachments of the levator aponeurosis. Design: Experimental anatomic study. Participants: Sixteen orbits from 12 fresh frozen white cadavers. Methods: Eight specimens served as controls. In the remaining 8 specimens from 4 cadavers, the upper eyelid was everted. All specimens then were fixed in formalin. The age, sex, and laterality were recorded in both groups. The eyelid lamellae and tarsal attachments of the levator aponeurosis in particular were examined microscopically. Lamellar and nonlamellar ocular anatomic features and the relationships of the preaponeurotic and postaponeurotic spaces were measured. Main Outcome Measures: Histologic findings of the extent and pattern of the tarsal attachments of the levator aponeurosis in relation to the tarsus and Müller's muscle and of the changes in the lamellae in eyelid eversion. Results: The demographic and baseline anatomic characteristics of both the noneverted control and everted eyelid groups were similar. In comparing everted with noneverted controls, the preaponeurotic space was significantly shorter (6.22 and 10.61 mm, respectively; P = 0.003) and the preaponeurotic-to-postaponeurotic space ratio was halved (0.57 and 1.16, respectively; P = 0.005). Although the distance from the superior tarsal border to Whitnall's ligament increased significantly in everted versus noneverted eyes (14.65 and 11. 03 mm, respectively; P = 0.016), there was no significant difference in the length of postaponeurotic space in the 2 groups (11.07 and 9.69 mm, respectively; P = 0.370). The levator aponeurosis attached to the anterior tarsus in both groups. The proximal point of attachment was the superior border of the tarsal plate, adjacent to the insertion of Müller's muscle tendon. Conclusions: The deeper aponeurotic fibers and Müller's muscle attach proximally at the superior tarsal border. Upon eyelid eversion, the 2 lamellae move as a unit and the postaponeurotic space remains stable. A proximal tarsal attachment suggests that blepharoptosis procedures that advance an involutional or disinserted levator aponeurosis onto to the superior tarsus approximate that aspect of native anatomic features. In addition, posterior surgical approaches that address Müller's muscle may involve resections in closer proximity to the aponeurosis than previously thought. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. © 2013 American Academy of Ophthalmology.

Cannon P.S.,South Australian Institute of Ophthalmology | Chan W.,South Australian Institute of Ophthalmology | Selva D.,South Australian Institute of Ophthalmology
Ophthalmology | Year: 2013

Purpose: To describe the incidence of canalicular closure with powered endonasal dacryocystorhinostomy (DCR) without canalicular intubation in primary acquired nasolacrimal duct obstruction (PANDO). Design: A single-surgeon, prospective, nonrandomized, noncomparative, interventional case series. Participants: Consecutive patients attending a specialist clinic of an oculoplastic surgeon (DS) with radiologically confirmed diagnosis of PANDO. Cases of canalicular disease were excluded. Methods: Patients with radiologically confirmed PANDO without canalicular involvement underwent endonasal DCR without intubation. The operation was performed by 1 surgeon (DS) and follow-up was at 4 weeks and 12 months. Main Outcome Measures: Outcomes were recorded as subjective symptomatic relief at 12 months and endoscopic evidence of ostium patency and canalicular patency. Results: There were 132 cases that fulfilled the inclusion criteria. Three cases were lost to follow-up. Preoperatively, 96.3% of cases had Munk scores of >2. Of the 129 cases, 127 (98.5%) had endoscopic evidence of a patent ostium with a positive endoscopic dye test at the 12-month follow-up. All cases had a patent canalicular system as demonstrated by syringing and probing. Of the 129 cases, 117 (90.7%) had subjective improvement of epiphora at 12 months with 88.4% of cases reporting Munk scores of ≤1. Conclusions: In this prospective series of nonintubation for PANDO, there were no cases of canalicular closure or stenosis at 12 months. Anatomic and functional success was similar to reported outcomes for DCR with intubation for PANDO. We advocate that routine intubation for the purpose of maintaining canalicular patency is not necessary when performing endonasal DCR in PANDO. © 2013 by the American Academy of Ophthalmology Published by Elsevier Inc.

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