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Aims: To determine whether the computerised version of the new aniseikonia test (NAT) is a valid, reliable method to measure aniseikonia and establish whether aniseikonia occurs in patients with epiretinal membranes (ERM) with preserved good visual acuity. Methods: With a computerised version of the NAT, horizontal and vertical aniseikonia was measured in 16 individuals (mean 47 (SD 16.46) years) with no ocular history and 14 patients (mean 67.7 (14.36) years) with ERM. Test validity was evaluated by inducing aniseikonia with size lenses. Test reliability was assessed by the test-retest method. Results: In normal individuals, the mean percentage (SD) aniseikonia was −0.24% (0.71) horizontal and 0% (0.59) vertical. Validity studies revealed mean (SD) 0.990 (0.005) horizontal and 0.991 (0.004) vertical correlation coefficients, 0.985 (0.111) horizontal and 0.989 (0.102) vertical slope. Repeatability coefficients were 1.04 horizontal and 0.88 vertical. Aniseikonia in patients with ERM ranged from 4% to 14%. Eight patients showed 2% or more size difference between horizontal and vertical meridians. Conclusions: The aniseikonia test used in this study can be considered a simple, fast, valid and reliable method to measure the difference in image size perceived by each eye. Aniseikonia does occur in symptomatic patients with ERM. The effect of ERM on image size is heterogeneous across the retinal area affected.

Aims: To establish the range of normal distance stereoacuity in young children using the Frisby Davis distance stereotest (FD2). Methods: Children passing preschool vision screening assessments underwent measurement of distance stereoacuity with the FD2 using a standard testing protocol. Results: 59 visually normal children aged between 36 months and 68 months were recruited to this study. All 59 were able to understand the test requirements and were examined with the FD2 stereotest. Four (6.8%) had no measurable stereoacuity; 13 (24%) had stereoacuity measurable only at a 3 metre testing distance (mean 92.3 seconds of arc; SD 52.6). These children were significantly younger than the remaining 42 (76%) who demonstrated a stereoacuity response at a 6 metre testing distance (mean 29.6 seconds of arc; SD 13.1, p = 0.008). Conclusion: The FD2 stereotest enables the measurement of distance stereoacuity in young children. There appears to be a maturational effect with distance stereoacuity improving between 36 months and 68 months. The data on age related normal values will provide a baseline from which to compare outcomes in clinical populations.

Ams: To describe the characteristics and surgical outcomes of full thickness macular hole surgery after laser assisted in situ keratomileusis (LASIK) for the correction of myopia. Methods: 13 patients (14 eyes) who developed a macular hole after bilateral LASIK for the correction of myopia participated in the study. Results: Macular hole formed 1–83 months after LASIK (mean 13 months). 11 out of 13 (84.6%) patients were female. Mean age was 45.5 years old (25–65). All eyes were myopic (range −0.50 to −19.75 dioptres (D); mean −8.4 D). Posterior vitreous detachment (PVD) was not present before and was documented after LASIK on 42.8% of eyes. Most macular hole were unilateral, stage 4 macular hole, had no yellow deposits on the retinal pigment epithelium, had no associated epiretinal membrane, were centric, and had subretinal fluid. The mean diameter of the hole was 385.3 μm (range 200–750 μm). A vitrectomy closed the macular hole on all eyes with an improvement on final best corrected visual acuity (VA) on 13 out of 14 (92.8%) patients. Conclusions: This study shows that vitreoretinal surgery can be successful in restoring vision for most myopic eyes with a macular hole after LASIK.

Aim: To assess the incidence and associated signs and symptoms of patients with keratoconus in Asir Province, Saudi Arabia. Methods: 125 new keratoconus patients (51 male, 74 female; mean age 18.5 (SD 3.8) years; range 8–28 years) were recruited from referrals to the department of ophthalmology, Asir Central Hospital, over a 1 year period. Age, visual acuity, and keratometry were recorded along with clinical signs and symptoms. Results: The incidence of keratoconus in Asir Province is 20 cases per 100 000 population. Also, the disease severity is high, as indicated by an early mean age (17.7 (3.6) years) with advanced stage keratoconus. Visual acuity, with either spectacles or rigid contact lenses, was 6/12 or better in 98% of eyes measured. Just over half (56%) of patients had atopic ocular disease. 16% of patients had a positive family history of the disease and 16% had atopic dermatitis (eczema and/or vitiligo). Conclusion: The incidence and severity of keratoconus in Asir Province, Saudi Arabia, is high with an early onset and more rapid progress to the severe disease stage at a young age. This might reflect the influence of genetic and/or environmental factor(s) in the aetiology of keratoconus.

Aim: To identify novel or rare rhodopsin gene mutations in patients with autosomal dominant retinitis pigmentosa and description of their clinical phenotype. Methods: The complete rhodopsin gene was screened for mutations by DNA sequencing in index patients. Mutation specific assays were used for segregation analysis and screening for controls. Eight patients from five families and their relatives were diagnosed with autosomal dominant retinitis pigmentosa (adRP) by means of clinical evaluation. Results: Mutation screening identified five different rhodopsin mutations including three novel mutations: Ser176Phe, Arg314fs16, and Val20Gly and two missense mutations, Pro215Leu and Thr289Pro, that were only reported once in a mutation report. Electrophysiological and psychophysical testings provide evidence of an impaired rod system with additionally affected cone system in subjects from each genotype group. Visual function tended to be less affected in subjects with the Arg314fs16 and Val20Gly mutations than in the Ser176Phe phenotype. In contrast, Pro215Leu and Thr289Pro mutations caused a remarkably severe phenotype. Conclusion: The ophthalmic findings support a correlation between disease expression and structural alteration: (1) extracellular/intradiscal Val20Gly and cytoplasmic Arg314fs16 mutation—mild adRP phenotype; (2) Ser176Phe mutation—“mostly type 1” disease; (3) predicted alteration of transmembrane domains TM V and TM VII induced by Pro215Leu and Thr289Pro—severe phenotype. However, variation of phenotype expression in identical genotypes may still be a typical feature of RHO mutations.

Aims: To examine the effectiveness of a management protocol for childhood epiphora using a joint ophthalmological and otolaryngological team approach. Method: A temporally defined retrospective study of 70 children (92 eyes) undergoing surgery for persistent epiphora, despite two previous technically successful probing procedures. All the operations involved a joint approach involving a paediatric ophthalmologist and a paediatric otolaryngologist. Results: In children with congenital nasolacrimal obstruction this joint approach yielded a 73% (89%) success rate, while in children with acquired nasolacrimal obstruction the success rate was 57%. Conclusions: Endonasal nasolacrimal intubation and endonasal DCR are safe and effective procedures for the management of persistent epiphora in children. They avoid the need for overnight admission and carry a minimal complication rate.

Background: Involvement of the eye has been reported in patients with variant Creutzfeldt-Jakob disease (vCJD), but there is disagreement on whether retinal involvement occurs in sporadic Creutzfeldt-Jakob disease (sCJD). Methods: Western blotting, paraffin embedded tissue blotting, and immunohistochemistry were used to test whether the abnormal form of the prion protein (PrPSc) accumulates to detectable levels in the eye in a case of the most common subtype of sCJD (MM1). Results: Low levels of PrPSc were detectable in the retina, localised to the plexiform layers of the central retina. PrPSc was not detectable in other ocular tissues. Conclusions: The abnormal form of the prion protein is present in the retina in the most common sCJD subtype (MM1), albeit at levels lower than those found previously in vCJD and in sCJD of the VV2 subtype.

Aim: To identify a gene linking microphthalmia with cyst with early onset medulloblastoma. Methods: Mutation analysis of the PTCH gene. Results: A mutation in exon 10 of the PTCH gene was identified, confirming a diagnosis of Gorlin syndrome. Conclusions: This is the first genetically identified mutation giving rise to microphthalmia with cyst and provides a valuable link in the eye developmental gene pathway.

Aims: To assess the diagnostic accuracy of optical coherence tomography (OCT), with/without colour fundus photographs, in predicting fundus fluorescein angiography (FFA) findings in patients suspected of havingchoroidal neovascularisation (CNV). Methods: A consecutive series of patients suspected of havingCNV underwent OCT and stereo FFA images, which were assigned a diagnosis by two masked observers, one examining OCT alone and then OCT plus stereo colour photographs, and one examining FFA alone. The main outcome measures were the diagnostic accuracy of OCT (with/without colour photos) in predicting the presence of CNV and secondly the characteristics of the CNV compared to the FFA findings. Results: 131 eyes of 118 patients were analysed. The sensitivity and specificity of OCT for detecting new potentially treatable CNV lesions compared to FFA was 96.4%, and 66.0%, respectively. For OCT with stereo images the sensitivity was 94.0% and specificity 89.4%. For detecting CNV with a classic component the sensitivity and specificity of OCT alone was 78.6% and 82.7%. With stereo colour images the sensitivity was 82.1% and specificity 89.3%. Conclusion: OCT is good at detecting the presence of CNV in patients suspected of having new CNV. However, it is less accurate at identifying the exact components of CNV. OCT cannot at present replace FFA in accurately diagnosing CNV components. However, this imaging method may have a role as a screening tool to help prioritise FFA requests.

Aims: To develop a minimally invasive, maximally effective method to biopsy anterior segment tumours. Methods: A 25 gauge aspiration cutter (vitrector) was used to biopsy anterior segment tumours. The probe was introduced under sodium hyaluronate 1% and through a 1 mm incision. Aspiration (600 mm Hg) cutting (300 cpm) was performed to obtain specimens for cytology and histopathology. Results: Diagnostic material was obtained in nine of 10 (90%) cases. Diagnoses included iris naevus, iris stroma, malignant melanoma, melanocytoma, epithelial inclusion cyst, and sarcoid granuloma. All corneal wounds were self sealing. One patient developed a transient postoperative increase in intraocular pressure. Within the follow up of this study, no patients suffered intraocular haemorrhage, infection, cataract or vision loss. Conclusion: The Finger iridectomy technique was a minimally invasive and very effective biopsy technique. Aspiration cutting yielded relatively large pieces of tissue (and cells) used for cytopathological and histopathological evaluation. Small incision surgery allowed for rapid rehabilitation and no significant complications.

Aim: To perform genealogical and clinical studies in Finnish families with X linked ocular albinism (OA1), including characterisation of the potential misrouting of optic fibres by evaluating visual evoked magnetic fields (VEFs), and to determine the mutation behind the disease. Methods: Three families with OA1 were clinically examined. VEFs were measured in two affected males and in one female carrier to characterise the cortical activation pattern after monocular visual stimulation. The neuronal sources of the VEFs were modelled with equivalent current dipoles (ECDs) in a spherical head model. All coding exons of the OA1 gene were screened for mutations by single strand conformation analysis and direct polymerase chain reaction sequencing. Results: Genealogical studies revealed that the three families were all related. The affected males had foveal hypoplasia with reduced visual acuity varying from 20/200 to 20/50, variable nystagmus, iris transillumination, and hypopigmentation of the retinal pigment epithelium. The ECD locations corresponding to the VEFs revealed abnormal crossing of the optic fibres in both affected males, but not in the carrier female. A novel point mutation, leading to a STOP codon, was identified in the fifth exon of the OA1 gene. Conclusions: The data indicate that the novel mutation 640C>T in the OA1 gene is the primary cause of the eye disease in the family studied. VEFs with ECD analysis was successfully used to demonstrate abnormal crossing of the optic fibres.

Aim: To investigate the cause of visual loss following removal of intraocular silicone oil in patients who underwent vitrectomies for retinal detachment or giant retinal tear. Methods: The clinical records of three cases with visual loss following removal of silicone oil were reviewed. Investigations carried out included fundus fluorescein angiogram, optical coherence tomography, and electrophysiological studies. Results: Visual acuities dropped from 6/9 to 6/36 in two cases and 6/24 to 3/24 in the third. None of the three cases had macula detachment at any stage. Fundus fluorescein angiogram and optical coherence tomography were normal in all cases. Pattern electroretinogram showed reduced amplitudes of the P50 and N95 components. Multifocal electroretinogram indicated a selective damage to the central part of the macula. Conclusions: The results suggest that the abnormality arises predominantly in the central part of the macula, especially the outer and middle layers. However, the exact mechanism still remains obscure., link_to_OA_fulltext

Aims: To determine the efficacy of sirolimus in the treatment of patients with severe non-infectious uveitis. Methods: Eight patients with severe non-infectious uveitis were recruited to an open study. Inclusion criteria were limited to patients whose disease was not controlled with at least two or more separate steroid sparing immunosuppressants (either because of unacceptable side effects or ineffectiveness of the drug) or who required regular doses of corticosteroids either as high dose systemic or orbital floor injections in order to control their disease. Intraocular inflammation, visual acuity, symptoms, corticosteroid burden, drug toxicity, and side effects were monitored. Results: Sirolimus therapy was effective in five of the eight patients, all of whom had their dose of corticosteroids reduced or discontinued. Treatment in three patients was considered a failure as it caused intolerable side effects and/or failed to control the uveitis. Side effects were common and were typically gastrointestinal or cutaneous in nature. The severity of symptoms was dose dependent in most cases and occurred at trough blood levels above 25 ng/ml. Conclusion: Sirolimus is an effective and potent immunosuppressive treatment in the majority of patients with non-infectious uveitis and can reduce the need for long term supplementary corticosteroid therapy. Further studies are required to establish the long term efficacy and safety of sirolimus alone or in combination with other steroid sparing immunosupressants.

Background/aims There is substantial evidence that mammalian epithelial stem cells are located within well defined niches. Although the corneoscleral limbus is acknowledged as the site of corneal epithelial stem cells no anatomical niche for such cells has yet been described. The authors undertook to re-evaluate the microanatomy of the limbus in order to identify possible sites that may represent a stem cell niche. Methods Systematic serial 5-7 microm sections of human corneoscleral segments obtained from cadaver donors, were examined. The sections were stained with haematoxylin and eosin or toludine blue. Sections with specific areas of interest were further examined immunohistologically for the corneal epithelial marker cytokeratin 14 and the "stem cell" marker ABCG2 transporter protein. Results Distinct anatomical extensions from the peripheral aspect of the limbal palisades were identified. These consist of a solid cord of cells extending peripherally or circumferentially. The cells stained positive for CK14 and ABCG2. Conclusions A novel anatomical structure has been identified at the human limbus, which demonstrates characteristics of being a stem cell niche. The authors have termed this structure the limbal epithelial crypt.

Aim: To report on a modified technique for upper eyelid lengthening in lid retraction associated with Graves’ disease. Methods: A prospective consecutive interventional case series. 41 patients, 38 women and three men, with a mean age of 55 years (range 32–75 years) were included. Full transsection of the upper eyelid with optional transsection of the lateral horn was performed in 60 lids. A central bridge of conjunctiva was left intact in the pupillary axis. Before and after surgery, the skin crease, palpebral aperture, and scleral show were measured and the contour of the lid margin was assessed. The overall result was graded as “perfect,” “acceptable,” and “failure.” Results: The mean period review was 6 months (range 2–36 months). Preoperatively, upper eyelid retraction varied from 1 mm to 7 mm; mean scleral show was 2 mm in 45 lids, the palpebral aperture was in the desired height (SD 1 mm) in 53 of 60 lids (88%) and was reduced by 3 mm (mean), the skin crease remained unchanged (SD 1 mm) in 44 of 60 lids (73%). The result was considered “perfect” in 43 and “acceptable” in 14 of 60 lids after one or two surgical approaches. In three lids, the surgery had failed. Conclusion: In contrast with other surgical techniques the surgical approach presented here is easy to perform and still leads to very satisfying and predictable postoperative results.

Aim: To determine whether there has been a consistent change across countries and healthcare systems in the frequency of strabismus surgery in children over the past decade. Methods: Retrospective analysis of data on all strabismus surgery performed in NHS hospitals in England and Wales, on children aged 0–16 years between 1989 and 2000, and between 1994 and 2000 in Ontario (Canada) hospitals. These were compared with published data for Scotland, 1989–2000. Results: Between 1989 and 1999–2000 the number of strabismus procedures performed on children, 0–16 years, in England decreased by 41.2% from 15 083 to 8869. Combined medial rectus recession with lateral rectus resection decreased from 5538 to 3013 (45.6%) in the same period. Bimedial recessions increased from 489 to 762, oblique tenotomies from 43 to 121, and the use of adjustable sutures from 29 to 44, in 2000. In Ontario, operations for squint decreased from 2280 to 1685 (26.1%) among 0–16 year olds between 1994 and 2000. Conclusion: The clinical impression of decrease in the frequency of paediatric strabismus surgery is confirmed. In the authors’ opinion this cannot be fully explained by a decrease in births or by the method of healthcare funding. Two factors that might have contributed are better conservative strabismus management and increased subspecialisation that has improved the quality of surgery and the need for re-operation. This finding has a significant impact upon surgical services and also on the training of ophthalmologists.

Background/aim: TGDc-01 is a new, portable, transpalpebral tonometry device. The aim of this study was to evaluate the reproducibility of this method, including intraobserver and interobserver deviations, and to compare the results with those of Goldmann applanation tonometry and palpation of intraocular pressure (IOP). Methods: A total of 40 eyes of 20 healthy volunteers were included. Two independent parallel observers (1 and 2) performed three replicate measurements per eye, respectively, both using TGDc01 tonometry, one observer (3) performed three replicate measurements using Goldmann applanation tonometry, and one observer (4) measured the IOP via palpation. Intraindividual deviations within and between both observers using TGDc-01 tonometry and between all three methods were investigated about clinically relevance by comparison of medians and quartiles, statistically significance by pairwise sign tests. Comparisons between observers and methods were based on averaged IOP values of the three individual measurements for each observer and each patient. Intraobserver deviations were analysed by means of Friedman tests. Results: Observers 1 and 2 showed a statistically significant intraobserver deviation when using TGCc-01 (Friedman p = 0.007 for observer 1 and p = 0.002 for observer 2). There was no statistically significant interobserver deviation between observers 1 and 2 (sign test p = 0.200); however, in 45% of the eyes interobserver deviations were larger than plus or minus 3 mm Hg. The median intraindividual deviation between TGDc-01 and Goldmann (TGDc-01 minus Goldmann) was 0 mm Hg (interquartile range −1; 2 mm Hg; sign test p = 0.522); but deviations were larger than plus or minus 3 mm Hg for 38% of the 40 eyes. Median intraindividual deviation between TGDc-01 and palpation (TGDc-01 minus palpation) was −2 mm Hg (interquartile range −4; 1 mm Hg; sign test p = 0.018), but deviations were larger than plus or minus 3 mmHg for 43% of eyes. Median intraindividual deviation between Goldmann and palpation (palpation minus Goldmann) was 2 mm Hg (interquartile range −2; 4 mm Hg; p = 0.429), but deviations were larger than plus or minus 3 mm Hg in 48% of the eyes. Conclusion: Interobserver deviations using TGDc-01 tonometry and intraindividual deviations between TGDc-01 tonometry, Goldmann applanation tonometry, and palpation of IOP were found to be clinically relevant. Thus, according to our results TGDc-01 could not be established as a substitute or diagnostic alternative method for Goldmann applanation tonometry. But as deviations between TGDc01 and Goldmann turned out smaller than between palpation of IOP and Goldmann, TGDc-01 seems to provide a better choice for tonometry in patients, in whom Goldmann applanation tonometry is not possible.

Aim: To investigate the effect of atorvastatin (Lipitor), a commonly used drug for dyslipidaemia in experimental autoimmune uveitis (EAU). Methods: 48 B10-RIII mice were immunised with human interphotoreceptor retinoid binding protein (IRBP) peptide p161–180. They were divided into three groups of 16 each and treated orally once daily for 14 days; group one received phosphate buffered saline (control group), group two received 1 mg/kg of atorvastatin (low dose group), and group three received 10 mg/kg (high dose). On day 14 lymph nodes, spleens, and right eyes were harvested. RNA was extracted from lymph nodes for RNase protection assay (RPA) to determine proinflammatory (IL-1α and IL-1β), Th1 (TNF-α, IL-2, IL-12), and Th2 (IL-4, IL-5, and IL-10) cytokine levels. Protein was extracted from spleens for western blot to detect the expression of phosphorylated signal transducer and activator of transcription (STAT) 4 and STAT6. The severity of inflammation in enucleated eyes was graded by a masked observer. Paired t test was performed for the mean difference in histological scoring between treated groups and the immunised control group. Results: Surprisingly, atorvastatin did not modulate the immune response. The proinflammatory cytokines, IL-1α and IL-1β, and Th1 cytokines, TNF-α and IL-2, were upregulated equally in control and atorvastatin treated groups. IL-12 and Th2 cytokines were not upregulated in all three groups. Western blot analysis showed high levels of phosphorylated STAT4, but not STAT6 protein in the control and atorvastatin treated groups. Mean differences in histological scoring between treated groups and the immunised control group were not statistically significant. Conclusions: Atorvastatin treatment had no effect on Th1 and Th2 cytokine transcription. Although histological grading suggested mildly decreased inflammation in the high dose treated group, the equivalence of cytokine expression in all groups suggests that the statins may not modulate IRBP induced uveoretinitis.

Aim: To investigate the relation between change in systemic blood pressures and change in intraocular pressure. Methods: This was a population based study of people 43–86 years old living in Beaver Dam, Wisconsin. Measurements at baseline (1988–90) and 5 year follow up of systemic blood pressures, intraocular pressures, and history of use of blood pressure medications. Results: Intraocular pressures were significantly correlated with systolic and diastolic blood pressures at both baseline and follow up. There were significant direct correlations between changes in systemic blood pressures and changes in intraocular pressure. There was a 0.21 (95% CI: 0.16 to 0.27) mm Hg increase in IOP for a 10 mm Hg increase in systolic and 0.43 (0.35 to 0.52) mm Hg increase in IOP for a 10 mm Hg increase in diastolic blood pressure. Further adjustment for diabetes and medication use did not alter these associations. Decreased systolic or diastolic blood pressures of more than 10 mm Hg over 5 years were significantly associated with decreased IOP. Conclusions: Reduced systemic blood pressure is associated with reduced intraocular pressure. This finding should be evaluated in other studies, especially with respect to the possibility of resultant decreased risk of open angle glaucoma.

Background: The authors recently identified three large genetically unrelated families with an identical 17 base pair duplication mutation in exon 4 of the PITX3 gene. Here, they report the detailed clinical phenotype. Methods: Affected and unaffected individuals in the three families with autosomal dominant posterior polar cataract underwent full clinical examination and donated blood samples for DNA extraction and molecular genetic studies. Results: In all three families, an identical 17 base pair duplication mutation in PITX3 was identified which co-segregated with disease status in the family. All affected individuals had bilateral progressive posterior polar cataracts. In one family, posterior polar cataract was the only clinical abnormality but in the other two families, one of 10 affected individuals and four of 11 affected individuals also had anterior segment mesenchymal dysgenesis (ASMD). Conclusion: Mutations in the PITX3 gene in humans result in posterior polar cataract and variable ASMD. The gene encodes a transcription factor which has a key role in lens and anterior segment development. The mechanism by which the mutant protein gives rise to such a regional pattern of lens opacity remains to be elucidated.

Aims: To evaluate the histology and function of Descemet’s membrane transplanted with intact endothelium. Methods: Japanese white rabbits and human eyebank eyes were used as donors and recipients of Descemet’s membrane transplantation. Donor endothelium was hydrodissected by injecting indocyanine green from a limbal incision, and then processed as a corneal scleral button. A 6 mm diameter donor sheet was trephined, and folded in half using a 6 mm diameter polymer as a carrier. Recipient endothelium was also hydrodissected from the limbus using trypan blue to stain the Descemet’s membrane. Continuous curvilinear descemetorhexis (CCD) was performed to remove a circular section of the Descemet’s membrane using a 27 gauge cystotome. Donor tissue was inserted into the anterior chamber through a 5 mm limbal incision and apposed to the host stroma. Polymers were removed following transplantation. Similar surgical procedures were performed in both rabbits and eyebank eyes. Haematoxylin eosin stains were performed after 28 days in rabbits, and eyebank eyes were fixed immediately following surgery for endothelial cell counts. Results: Rabbit control eyes demonstrated stromal oedema caused by loss of Descemet’s membrane, whereas transplanted eyes had clear corneas. The mean (standard deviation) pachymetry of operated eyes was 376.6 (SD 32.5) μm compared with 389.6 (SD 25.1) μm in the unoperated eye. Mean endothelial density immediately following surgery in eyebank eyes was 2749 (SD 288) cells/mm2. Conclusions: Transplantation of Descemet’s membrane by CCD produces a functional graft with an optically clear interface similar to control cornea.

To investigate the effects of oral nimodipine on ocular haemodynamic parameters and colour contrast sensitivity in patients with normal tension glaucoma (NTG).The study was performed in a randomised, placebo controlled, double masked, crossover design.Nimodipine (60 mg) or placebo was administered to 14 consecutive NTG patients.The effects or oral nimodipine or placebo on ocular and systemic haemodynamic parameters and colour contrast sensitivity along the tritan axis were studied two hours after administration. Optic nerve head blood flow (ONHBF) and choroidal blood flow (CHBF) were assessed with laser Doppler flowmetry. Ocular fundus pulsation amplitude (FPA) was measured with laser interferometry. Colour contrast sensitivity (CCS) was determined along the tritan colour axis.ONHBF, CHBF, FPA, intraocular pressure and CCS were assessed in patients with NTG.Mean ocular FPA increased by 14% (SD 14%) (p = 0.0008), ONHBF by 18% (SD 16%) (p = 0.0031), and CHBF by 12% (SD 14%) (p0.001) after administration of nimodipine. Nimodipine also decreased the threshold of colour contrast sensitivity along the tritan colour axis (-14% (SD 12%); p = 0.048). However, individual changes in FPA, ONHBF, or CHBF were not correlated with changes in threshold of CCS along the tritan colour axis.The results indicate that nimodipine increases ONH and choroidal blood flow in NTG patients and improves CCS. The latter effect does not, however, seem to be a direct consequence of the blood flow improvement.

This study examines the changes in axial length (AL) after trabeculectomy and glaucoma drainage device (GDD) surgery and enabled an equation to be derived allowing prediction of AL change after filtering surgery.This was a prospective, interventional case series from the Glaucoma Service of the Doheny Eye Institute.One eye of 39 patients undergoing trabeculectomy and 22 undergoing Baerveldt tube shunt implantation for uncontrolled glaucoma.These patients had AL measurements by non-contact, partial coherence interferometry preoperatively, at 1 week, 1 month, and3 months after surgery.Axial length and intraocular pressure were compared at preoperative and postoperative visits. Postoperative intraocular pressure (IOP) was categorised as hypotonous (0-4 mm Hg), low (5-9), normal (10-17), and high (18 or more).There was a statistically significant reduction in IOP after 3 months of -12.8 (SD 1.5) mm Hg following trabeculectomy (p0.001), and -10.7 (1.9) mm Hg after GDD (p0.001). There was a statistically significant reduction in AL, which was similar after trabeculectomy and GDD at all time points (p0.001), of -0.15 (0.03) and -0.21 (0.04) mm (1 week), -0.18 (0.02) and -0.10 (0.02) mm (1 month), and -0.16 (0.03) and -0.15 (0.03) mm (3 months). At 3 months or later the AL reduction was related to postoperative IOP and to the amount of IOP reduction (p0.05, stepwise multiple regression). 10.2% (4/39) of trabeculectomy patients had hypotony after 3 months, with a mean AL reduction (-0.39 (0.11)) that was statistically significantly lower (p0.01) than the other trabeculectomy eyes (-0.14 (0.15)).There is a small but statistically significant decrease in AL after both trabeculectomy and GDD surgery, greater in eyes that are hypotonous after surgery. The authors suggest that AL reduction can be predicted after 3 months by the formula: AL reduction (mm) = -199+0.006 x IOP reduction+0.008 x final IOP.

Background/aim: Retinoblastoma is the commonest primary intraocular tumour in children. Chemotherapy now plays a big part in the treatment of these tumours. There is not much information about the role of the multidrug resistance proteins (MDR)—P-glycoprotein (P-gp) and vault protein lung resistance protein (LRP)—in retinoblastoma. The authors investigated the expression of P-gp and LRP in retinoblastoma and correlated them clinicopathologically. Methods: Among 60 retinoblastomas, 40 tumours were not subjected to preoperative or postoperative chemotherapy and 20 tumours were subjected to postoperative chemotherapy. In this cohort 27 tumours had no invasion and 33 tumours had invasion of choroid, optic nerve, and orbit. P-gp and LRP expression were studied by immunohistochemistry. Immunoanalysis was done semiquantitatively. Results: Among the 60 tumours P-gp was expressed in 23 (38%) tumours and LRP was expressed in 35 (58%). P-gp was expressed in 11/27 (40%) tumours with no invasion and in 12/33 (36%) tumours with invasion. LRP was expressed in 15/27 (55%) tumours with no invasion and in 20/33 (60%) tumours with invasion. Both P-gp and LRP were negative in three tumours with invasion, which had later developed bone marrow metastasis. There was no correlation between P-gp and LRP expression with invasion, differentiation and laterality of the tumours and response to treatment. Conclusion: Retinoblastoma expresses P-gp and LRP intrinsically before chemotherapy and none of these proteins predicted the response to chemotherapy. Thus, further studies are needed to understand the significance of the expression of the P-gp and LRP proteins in retinoblastoma.

Aims: To investigate the clinical observations that arteriovenous shunts typical of threshold retinopathy of prematurity (ROP) are morphologically different in extremely low birthweight infants weighing less than 1000 g. Methods: An observational case series of six extremely low birthweight infants displaying specific features of threshold retinopathy of prematurity enrolled between 1998 and 2001 at one centre. The variant morphology was documented with colour photography and fundus fluorescein angiography before laser therapy. Results: Stage 3 threshold ROP in extremely premature infants may be characterised by a different morphology not demonstrating classic shunt formation. A poorly developed capillary bed is present in already vascularised retina in these cases. Conclusions: This case series of extremely low birthweight infants display variations in the typical morphological appearance of threshold ROP. In these cases, established plus disease may be present in the absence of arteriovenous shunting. Delaying treatment until a classic stage 3 ridge with extraretinal neovascularisation develops may be detrimental to controlling the disease process. The authors propose that the criteria for threshold disease requiring treatment do not accurately apply in this extremely low birthweight group as defined by the CRYO-ROP study and that treatment should be instituted before the typical threshold features arise. Plus disease remains the most reliable sign indicating the need for treatment.

Background: Proliferative diabetic retinopathy (PDR) may be a response to abnormal angiogenic growth factors such as vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2), and the soluble angiopoietin receptor tie-2. The authors hypothesised the following: (a) there are differences in plasma levels of these growth factors in different grades of diabetic retinopathy; and (b) that the effects of intervention with panretinal laser photocoagulation (PRP) for PDR, and angiotensin receptor blockade (using eprosartan) for patients with other grades of diabetic retinopathy will be to reduce levels of the growth factors. Methods: Cross sectional and interventional study (using PRP and eprosartan) in diabetic patients. VEGF, Ang-2, and tie-2 were measured by ELISA. Results: VEGF (p

Background/aims: In uveal melanoma monosomy 3 is emerging as a significant indicator of a poor prognosis. To date most cytogenetic studies of uveal melanoma have utilised fresh tissue or DNA extracted from tissue sections. In this study chromosome in situ hybridisation (CISH) was used to study monosomy 3 in tissue sections. The copy number of chromosome 3 was determined and related to patient survival. Methods: Archival glutaraldehyde or formalin fixed, paraffin embedded material was obtained from 30 metastasising and 26 non-metastasising choroidal melanomas. Hybridisations were performed using centromere specific probes to chromosomes 3 and 18. Chromosome 18 was included as a control as previous abnormalities in uveal melanoma have not been described. Chromosomal imbalance was defined on the basis of changes in both chromosome index and signal distribution. Results: CISH was successfully performed on both glutaraldehyde and formalin fixed tissue. Four cases were unsuccessful because of extensive tumour necrosis. All cases were balanced for chromosome 18. Monosomy 3 was detected in 15 of the 26 cases of metastasising melanoma; the 26 non-metastasising tumours were all balanced for chromosome 3. Monosomy 3 was significantly associated with metastases related death. Conclusion: CISH can successfully identify monosomy 3 in archival glutaraldehyde or formalin fixed, paraffin embedded tissue sections. Similar to previous studies monosomy 3 is a significant predictor of metastases related death.

Aim: To determine utilisation patterns and calculate treatment failure and discontinuation rates in patients with open angle glaucoma treated in the United Kingdom with any of six groups of intraocular pressure (IOP) lowering agents. Methods: The UK General Practice Research Database was used to identify newly diagnosed (after 1 January 1997) open angle glaucoma patients who were naive to therapy with any of six index drug groups: carbonic anhydrase inhibitors, latanoprost, miotics, sympathomimetics, timolol, and other (non-timolol) β blockers. Analyses included drug treatment data for 1 year following diagnosis. Outcomes were (1) time to therapy failure, defined as either change in index drug (replacement or addition of therapy) or patient referral for surgery, and (2) time to therapy discontinuation, defined as either therapy failure or no refill of the index drug in a period twice that covered by the first prescription fill. Cox proportional hazard regression and Kaplan-Meier and life table methods were used to compare groups. Results: Among the 2001 eligible patients, a β blocker other than timolol was the most widely prescribed (42%), followed by timolol (32%), carbonic anhydrase inhibitors (10%), and latanoprost (7%). Compared to latanoprost, those treated with any alternative agent were significantly more likely to fail (p⩽0.005 for each comparison) and to discontinue (p⩽0.05 for each comparison) therapy. Failure rates ranged from 13% (latanoprost) to 45% (sympathomimetics), and discontinuation rates ranged from 30% (latanoprost) to 63% (miotics). Conclusion: Latanoprost treated patients demonstrated lower rates of therapy failure and therapy discontinuation compared with patients treated with other widely used IOP lowering medications, including β blockers.

Background/aim: To compare intraocular pressure (IOP) measurements taken by the Goldmann applanation tonometer, the Tono-Pen and the ocular blood flow pneumotonometer in eyes with varying central corneal thickness (CCT) due to penetrating keratoplasty (PK), keratoconus (KC), and Fuchs’ endothelial dystrophy (FED). Methods: IOP was measured with the Goldmann applanation tonometer, Tono-Pen XL, and OBF pneumotonometer in 127 eyes with the following corneal abnormalities. There were 56 eyes that had undergone PK, 37 eyes with KC, and 34 eyes with FED. CCT was measured using an ultrasound pachymeter after IOP determinations had been made. Results: Mean IOP measurements in all three patient groups were significantly higher when measured by OBF pneumotonometer. Linear regression analysis showed that patients with FED had a significant increase in IOP with increasing CCT of 0.18 mm Hg/10 μm using the Goldmann tonometer, 0.15 mm Hg/10 μm with the Tono-Pen, and 0.26 mm Hg/10 μm with the OBF pneumotonometer. In patients with KC and after PK, linear regression analysis did not show a significant effect of CCT on IOP. A multivariate linear regression model controlling for age, sex, graft size, and patient group, showed that the effect of CCT on IOP for Tono-Pen (0.13 mm Hg/10 μm CCT) and Goldmann (0.14 mm Hg/10 μm CCT) were significantly lower than for the OBF pneumotonometer (0.26 mm Hg/10 μm CCT). Conclusions: This study found that mean IOP measurements using the OBF pneumotonometer were significantly higher than those made using the Goldmann applanation tonometer or Tono-Pen in eyes with a variety of cornel pathologies. The OBF pneumotonometer was found to be most affected by variation in CCT. For all three instruments, the relation between IOP and CCT depended on the corneal pathology and was greatest for FED.

Aim: To evaluate efficacy of verteporfin ocular photodynamic therapy (PDT) in treatment of 10 patients with a symptomatic circumscribed choroidal haemangioma. Design: Prospective non-randomised, interventional case series and critical review of previously published studies. Methods: 10 consecutive patients (seven primary, two failed transpupillary thermotherapy (TTT), and one failed external beam radiotherapy) with symptomatic circumscribed choroidal haemangioma were treated using verteporfin 6 mg/m2 given as an intravenous infusion over 10 minutes. Diode laser (690 nm) with an intensity of 600 mW/cm2 for 83 seconds (50 J/cm2) was applied 5 minutes after completion of infusion. Single or multiple partially overlapping spots were applied based on the tumour basal dimensions. Periodic follow up with ophthalmoscopy, ultrasonography, and angiographic studies was performed. Results: All 10 patients showed evidence of regression with flattening of tumour, resolution of subretinal fluid, and reduction of choroidal vasculature on angiograms. The visual acuity either improved or remained stable in eight (80%) patients. Visual loss due to delayed choroidal atrophy was seen in two patients. Conclusions: Although verteporfin PDT is an effective treatment for management of symptomatic circumscribed choroidal haemangioma, delayed treatment related effects can lead to visual loss.

Aims: (1) A prospective study to assess visual function measures and quality of life (QoL) in patients with wet age related macular degeneration (AMD) treated with photodynamic therapy (PDT). (2) To assess if PDT prevents severe visual loss (loss of six or more lines of distance visual acuity) in the treated eye. Methods: 48 of 51 recruited patients with predominantly classic subfoveal choroidal neovascularisation (CNV) secondary AMD who were treated with PDT were followed up for 1 year. Assessment included distance and near visual acuity, contrast sensitivity, vision related quality of life and fluorescein angiography. Photodynamic therapy using Visudyne was carried out according to standard protocol. Patients were followed up every 3 months and treatment repeated if there was significant leakage from CNV. Results: At the 12 month follow up, 71% (n = 34) of the patients lost less than three lines of best corrected distance visual acuity. Although there were significant decreases in some of the QoL items tested, patients were significantly less anxious and more independent outdoors at the 12 month follow up. Conclusion: This study is in keeping with published literature with PDT preventing severe visual loss in two thirds of treated patients with predominantly classic CNV.

Aim: To devise a simple, robust scoring system for assessing the risk of intraoperative complications in patients undergoing cataract surgery. Methods: 1441 consecutive patients undergoing phacoemulsification cataract surgery were assessed preoperatively according to weighted criteria. According to the points of risk they accumulated using this system, the patients were preoperatively allocated to one of four risk groups. Data were prospectively collected on the occurrence of intraoperative complications and entered into a computerised database. The total rate of intraoperative complications for each risk group as well as the rate of each reported complication for each risk group were calculated. Results: The rate of intraoperative complications increased in frequency through the risk groups: 1 = 4.32%, 2 = 7.45%, 3 = 13.48%, and 4 = 32.00% (p Conclusion: These results suggest that candidates for cataract surgery can be simply and uniformly assessed preoperatively and categorised to a “risk group” according to their risk of intraoperative complications. This allows for: (1) individualised counselling on the chances of operative complications, (2) meaningful comparisons between national complication rates and those of individual units or surgeons, and (3) better selection of cases suitable for instruction.

Background: Recently, in patients with normal tension glaucoma (NTG) elevated levels of antiphosphatidylserine antibodies (APSA), a subgroup of antiphospholipid antibodies (APLA) were found. Progressive sensorineural hearing loss (PSHL) is associated with autoimmune diseases and also the presence of APLA. Methods: To investigate a possible association between NTG and PSHL, 34 patients (age range 31–81 years) with NTG were evaluated for evidence of audiovestibular disorders. Besides ophthalmological standard examinations (slit lamp, IOP, funduscopy, perimetry) scanning laser tomography and polarimetry were performed. From all patients’ audiograms, stapedial thresholds and otoacoustic emissions were obtained. The serological testing of patients and controls (40 healthy blood donors older than 50 years) concerned IgG and IgM levels of antibodies against phosphatidylserine (APSA) and β2 glycoprotein. Results: 23 of 34 NTG patients had hearing loss (PSHL n = 11; presbyacusis n = 12). The NTG patients had significantly higher APSA levels than controls. Elevated APSA concentrations were significantly more frequent in patients with NTG and hearing loss compared with NTG patients with normacusis. Conclusions: These findings show that NTG and hearing loss have a high coincidence. The elevated APSA levels may indicate an association with similar systemic autoimmune processes.

Aim: To investigate L-selectin expression and shedding in patients with and without retinopathy and to determine if any observed changes are reflected by a functional change in the adhesion of leucocytes to an endothelial monolayer. Methods: Age matched diabetic patients (26 with retinopathy, 19 without retinopathy) were compared to 24 non-diabetic controls to determine L-selectin surface protein expression, L-selectin mRNA production, and serum L-selectin levels by flow cytometry, RT-PCR, and ELISA, respectively. An adhesion assay was used to determine the binding of lymphocytes from the respective test groups to a monolayer of human endothelial cells. Results: Significantly reduced (p = 0.004) L-selectin expression was demonstrated on lymphocytes (CD3+) from patients with diabetes compared to controls, the lowest levels being found in those with diabetic retinopathy (p = 0.004). L-selectin mRNA levels (p = 0.007) were significantly higher in the retinopathy group than in the no retinopathy group. Serum L-selectin levels were significantly higher (p = 0.04) in those with retinopathy compared to controls. Lymphocyte adhesion relative to control (100%) was essentially unchanged (84.0% (SD 27.7%), p = 0.15) for diabetic patients with no retinopathy and was markedly increased (192% (37.6%)) for those with retinopathy (p = 0.0001). Conclusion: Lymphocyte activation, reduced surface L-selectin, increased circulating L-selectin, and a corresponding increase in adhesion of patients’ cells using an in vitro assay, is evident in people with diabetic retinopathy. This suggests a role for lymphocyte activation in the pathogenesis of diabetic retinopathy.

To determine the indications for penetrating keratoplasty (PK) at the Corneoplastic Unit and Eye Bank, UK, a tertiary referral centre, over a 10 year period.Records of all patients who underwent PK at our institution between 1990 and 1999 were reviewed retrospectively. Of the 1096 procedures performed in this period, 784 records were available for evaluation (72%).Regrafting was the most common indication, accounting for 40.9% of all cases. Keratoconus was the second most common indication (15%), followed by Fuchs' endothelial dystrophy (9.3%), pseudophakic bullous keratopathy (7.6%), and viral keratitis (5.9%), which included both herpes simplex and herpes zoster and showed a statistically significant decreasing trend using regression analysis (p0.005). Among the regraft subgroup, viral keratitis accounted for 21.2% as the underlying primary diagnosis. The most common cause for graft failure in the regraft subgroup was endothelial failure (41.8%).Regrafting is the leading indication for PK; viral disease-although declining-is the leading primary diagnosis.

To compare trabeculectomy with viscocanalostomy augmented with adjunctive antimetabolite use for the control of intraocular pressure (IOP) in open angle glaucoma (OAG).45 patients (50 eyes) with uncontrolled OAG were randomised to either trabeculectomy (25 eyes) or a viscocanalostomy technique (25 eyes). Preoperatively, all eyes were graded in terms of risk factors for drainage failure and were given intraoperative antimetabolites (5-fluorouracil 25 mg/ml (5-FU), mitomycin C (MMC) 0.2 mg/ml and 0.4 mg/ml) according to a standard protocol.There were no significant differences between the groups in age, sex, type of OAG, preoperative medications, risk factors for drainage failure, and preoperative IOP. Mean follow up was 20 months (range 3-24 months). It was 12 months or longer in all eyes, except two lost to follow up at 3 months. At 12 months, complete success (IOP21 mm Hg without antiglaucoma medications) was seen in 91% of eyes undergoing trabeculectomy, but in only 60% of eyes undergoing viscocanalostomy (p0.02). Similarly, at the last follow up visit (mean 20 months) complete success was seen in 68% of eyes undergoing trabeculectomy and 34% with viscocanalostomy (p0.05). In terms of qualified success (IOP21 mm Hg with or without glaucoma medications) and mean IOP measurements postoperatively there were no difference between the groups, although the mean number of antiglaucomatous medications required postoperatively was less with trabeculectomy (0.39) than viscocanalostomy (1.04) (p0.05). Needling procedures were more commonly required after trabeculectomy (p0.02). YAG goniotomy was required in three eyes (13%) after viscocanalostomy. Early transient complications such as anterior chamber shallowing and encysted blebs were more common in the trabeculectomy group (p0.05). Late postoperative cataract formation was similar between the two groups.In terms of complete success and number of antiglaucomatous medications required postoperatively, IOP control appears to be better with trabeculectomy. Viscocanalostomy is associated with fewer early transient postoperative complications.

Stimulation of the retina with flickering light increases retinal arterial and venous diameters in animals and humans, indicating a tight coupling between neural activity and blood flow. The aim of the present study was to investigate whether this response is altered in patients with insulin dependent diabetes mellitus.26 patients with diabetes mellitus with no or mild non-proliferative retinopathy and 26 age and sex matched healthy volunteers were included in the study. Retinal vessel diameters were measured continuously with the Zeiss retinal vessel analyser. During these measurements three episodes of square wave flicker stimulation periods (16, 32, and 64 seconds; 8 Hz) were applied through the illumination pathway of the vessel analyser.In retinal arteries, the response to stimulation with diffuse luminance flicker was significantly diminished in diabetic patients compared to healthy volunteers (ANOVA, p0.0031). In non-diabetic controls flicker stimulation increased retinal arterial diameters by +1.6% (1.8%) (mean, p0.001 v baseline), +2.8% (SD 2.2%) (p0.001) and +2.8% (1.6%) (p0.001) during 16, 32, and 64 seconds of flicker stimulation, respectively. In diabetic patients flicker had no effect on arterial vessel diameters: +0.1% (3.1%) (16 seconds, p = 0.9), +1.1% (2.7%) (32 seconds, p = 0.07), +1.0% (2.8%) (64 seconds, p = 0.1). In retinal veins, the response to flicker light was not significantly different in both groups. Retinal venous vessel diameters increased by +0.7% (1.6%) (16 seconds, p0.05), +1.9% (2.3%) (32 seconds, p0.001) and 1.7% (1.8%) (64 seconds, p0.001) in controls during flicker stimulation. Again, no increase was observed in the patients group: +0.6% (2.4%), +0.5% (1.5%), and +1.2% (3.1%) (16, 32, and 64 seconds, respectively).Flicker responses of retinal arteries and veins are abnormally reduced in patients with IDDM with no or mild non-proliferative retinopathy. Whether this diminished response can be attributed to altered retinal vascular reactivity or to decreased neural activity has yet to be clarified.

Aim: To confirm the prognostic value of post-brachytherapy initial tumour regression rate in posterior uveal melanoma. Methods: A prospective, comparative, observational cohort study was carried out on 147 eyes (147 patients) with choroidal melanoma (mean age 61 years) treated with Ru-106 brachytherapy. Observation procedure: Patients were followed clinically and ultrasonically every 6.7 (SD 0.3) months (1001 examinations). On average each patient was examined 5.8 times (mean follow up 9.6 (3.7) years). The echographic parameters included tumour base size, height, internal reflectivity, regularity, vascularity, and extrascleral extension. The clinical follow up included ocular examination and periodic metastatic screening (liver function tests and liver imaging). Main outcome measures were risk of liver metastasis in correlation with the post-brachytherapy initial tumour regression rate. Results: At brachytherapy the mean tumour height was 5.2 mm (range 2.2–11.8 mm). After brachytherapy 142 tumours (96.6%) responded by a decrease in height. The initial height regression rate was 6.1% (0.8%) per month in patients who later developed metastasis v 4.3% (0.4%) per month in those who did not. Tumours higher than 6 mm, tumours with an internal reflectivity smaller than 50%, and tumours with an initial rate of height regression larger than 0.7 mm/month (10% per month) had higher 5 year melanoma related mortality. Kaplan-Meier survival analysis and the multivariate Cox proportional hazards model showed a significant role for tumour height and initial tumour regression rate on patients’ survival. Conclusion: This study confirms that post-brachytherapy initial tumour regression rate has a prognostic value.

Aims: Mare’s tail lines are uncommon, grey, parallel, tapering epithelial lines, which may give rise to discomfort or to visual symptoms. The authors report the clinical and ultrastructural findings in two patients Methods: Therapeutic debridement was performed in two patients suffering from mare’s tail disorder. The loosely attached epithelium was removed and fixed in glutaraldehyde containing cuprolinic blue and processed in a standard fashion for electron microscopy. Results: Ultrastructural studies showed an avascular, collagenous pannus extending under the whole of the excised epithelium in each case and separated from it by a thickened basal lamina like zone. The basal laminar material extended into the epithelium in folds, in keeping with the clinical features. Interesting ultrastructural features included: (1) a lack of hemidesmosomes in relation to the basal laminar material; (2) trapping of degenerate keratocytes within the invaginating basal laminar folds; (3) an unusual regularity and fine dimensions of the collagen fibrils and proteoglycans making up the subepithelial pannus. The basal laminar material contained proteoglycans and small fibres similar in appearance to long spacing collagen. Conclusions: Mare’s tail lines are caused by basal laminar material, assumed to be chiefly of epithelial origin, which invaginates the corneal epithelium. The presence of occasional keratocytes within the invaginating folds suggests that there may be a stromal contribution to the disorder. The visibility of mare’s tail lines in the focal beam of the slit lamp is likely to be related to the thickness and light scattering properties of the invaginations and of the subepithelial deposits. Tractional forces, imposed by lid action, could explain their horizontal disposition.

Purpose: The development of posterior capsule contraction following cataract surgery is caused by the activity of residual lens epithelial cells. Matrix metalloproteinases (MMPs) are a group of proteolytic enzymes, which are essential for cell migration and cell mediated contraction following wound healing. The authors investigated whether inhibiting MMP activity can reduce lens epithelial cell migration and as a result, lead to a reduction in cell mediated capsule contraction. Methods: Human donor lens capsules were cultured and treated with a broad spectrum MMP inhibitor, Ilomastat (GM6001). MMP-2 and MMP-9 production were determined by ELISA. Cell migration onto the posterior capsule and capsule contraction were digitally measured. Results: MMP inhibition significantly reduced lens epithelial cell migration onto the posterior capsule (p

Background: To investigate the levels of nitric oxide (NO) markers in plasma and aqueous humour of patients with primary open angle glaucoma (POAG) and their relation to ocular perfusion pressure. Methods: Cyclic guanosine monophosphate (cGMP) and nitrite (NO2−) were determined in plasma and aqueous humour of 38 patients with POAG and 46 controls. Blood pressure and IOP were measured to calculate ocular perfusion pressure (PP). Results: cGMP and NO2− plasma levels were significantly decreased in glaucoma patients compared with controls (p = 0.001 v p = 0.004). In the aqueous humour of subjects with POAG, cGMP and NO2− concentrations were also lower than in normal eyes (p = 0.0001 v p = 0.001). There was a linear association between cGMP in plasma and aqueous humour in glaucomas and controls (r = 0.514, p = 0.029 and r = 0.558, p = 0.004) and this relation differed in the two groups (p = 0.003). Considering glaucoma patients with controls, a positive correlation was found between cGMP and PP (r = 0.379, p = 0.01) and between NO2− and PP (r = 0.339, p = 0.040). The cGMP/PP correlation was of borderline statistical significance in controls (p = 0.050), whereas it did not attain statistical significance in POAG, as well as the association between NO2− and PP when glaucomas and controls were considered separately. Conclusions: The authors found alterations of NO markers in the plasma and aqueous humour of glaucoma patients. Primary or secondary impaired NO balance could alter ocular perfusion pressure.

Objective: The 97.5th percentile for vertical cup to disc ratio (VCDR) has been proposed as a useful tool to assist in the diagnosis of glaucoma in population studies. Previous reports of VCDR percentiles have either not been adjusted for disc size or have been calculated by regression analysis from small hospital based cohorts. The authors’ aim was to generate VCDR percentiles in a large, population based sample. Methods: Data were collected from 3654 individuals, aged 49 years or older, living in the Blue Mountains, west of Sydney. Vertical disc diameter and VCDR were determined by planimetry from stereo optic disc photographs. The distribution of VCDR and percentiles (95th, 97.5th, 99th) were calculated. Results: 6678 eyes were included in the analysis. Median cup to disc ratio, 95th, 97.5th, and 99th percentile increased with vertical optic disc diameter in a linear fashion. An increase of 0.2 in median VCDR (0.35 to 0.55) was observed between small (1.1–1.3 mm) and large (1.8–2.0 mm) optic discs. An equivalent increase of 0.2 (0.59 to 0.74) was observed for the 97.5th percentile from small to large discs. Conclusion: VCDR percentiles for a “normal” population, adjusted for vertical optic disc diameter are presented. One quarter of all discs fell within the small or large disc categories highlighting the importance for estimating optic disc size. These data may assist in the diagnosis of glaucoma in clinical practice as well as providing a normative database. Sole use of VCDR percentile cut offs in defining glaucoma cases in population surveys requires further validation.

To quantify retinal vascular change during and after hyperbaric oxygenation (HO) for 6x5 weekly 90 minute treatments.Fundus photographs were taken before, during, and after HO at 2.5 atmospheres absolute pressure (ATA) on days 1, 2, 3, 10, 20, 29, and 30 of treatment on three patients using a specially developed hand held ophthalmoscope with a digital colour camera. Blood vessel diameter was estimated on red free retinal images. The mean of three measurements of arterioles and venoles close to the optic disc was calculated. Consistency and repeatability of the method was verified by estimating the diameter of the vessels by three measurements in each of seven images taken within 70 seconds on the same person. Analysis of variance with Bonferroni correction for multiple comparisons was conducted to ascertain whether significant intergroup differences existed.Breathing 100% oxygen at 2.5 ATA constricts retinal arterioles by 9.6% (standard deviation 0.3%) and venoles by 20.6% (SD 0.3%) of their size in air at ambient pressure. Constriction escalates during treatment. Ten minutes after the HO, arterioles dilate to 94.5% (SD 0.3%) and venoles to 89.0% (SD 0.3%) of their primary size. This pattern is the same for each day of measurement. Heart frequency falls continually during HO. Systolic, diastolic, and mean arterial pressures stay constant.Exposure to hyperbaric oxygen causes constriction of the retinal vessels. It is found that this constriction is constant through the series of treatments. This suggests that oxygen or products thereof are responsible for the vascular changes during and after hyperbaric oxygenation probably through autoregulation of the retinal vessels.

To investigate a potential difference in ocular vascular reactivity during carbogen breathing in optic nerve head, choroid, and retina between healthy smokers and non-smokers.25 (13 smokers and 12 non-smokers) healthy male volunteers participated in this observer masked, two cohort study. During inhalation of carbogen (5% CO(2) and 95% O(2)) over 10 minutes measurements were taken using laser Doppler flowmetry to assess submacular choroidal and optic nerve head blood flow, laser interferometry to assess fundus pulsation amplitudes, and retinal vessel analyser (RVA) to assess retinal vessel diameters.At baseline choroidal blood flow was higher (p = 0.018, ANOVA) in smokers than in non-smokers. During administration of carbogen the response in choroidal blood flow was significantly different between the two groups: there was an increase in non-smokers after carbogen breathing (p = 0.048) compared with relatively stable blood flow in smokers (p = 0.049 between groups, ANOVA). A similar response pattern was seen for fundus pulsation amplitude, which increased notably after carbogen breathing in non-smokers but not in smokers (p0.001 between groups, ANOVA). Optic nerve head blood flow and retinal vessel diameters were reduced in both groups to a comparable degree during carbogen breathing.The study indicated abnormal choroidal vascular reactivity in chronic smokers. These early haemodynamic changes may be related to the increased risk to smokers of developing ocular vascular diseases. The specific mechanisms underlying abnormal choroidal vascular reactivity in chronic smokers remain to be characterised.

Aims: To compare the postoperative performance of single and three piece acrylic foldable intraocular lenses (IOLs). Methods: 20 patients underwent bilateral cataract surgery with a single piece SA30AL IOL in one eye and a three piece MA30BA IOL in the other eye. The eyes were randomly assigned to either a single or three piece lens. The amount of IOL decentration and tilt, area of anterior capsule opening, and degree of posterior capsule opacification were measured using the Scheimpflug anterior segment analysis system (Nidek EAS-1000). Visual acuity and contrast sensitivity were examined. Measurements were performed by masked examiners before and 1 day, 1 week, 1, 3, 6, and 18 months after surgery. Results: There were no significant differences between the two groups (p>0.05, paired t test) in the amount of IOL decentration, IOL tilt, area of anterior capsule opening, degree of posterior capsule opacification, best corrected visual acuity, and contrast sensitivity throughout the 18 month follow up period. Conclusion: The single and three piece acrylic foldable IOLs are equally stable in the eye after surgery.

Background/aims: Doxycycline is a broad spectrum antibiotic that chelates metal ions and is frequently used as part of the treatment of ocular surface diseases. Its therapeutic value has been ascribed to an ability to inhibit matrix metalloproteinase (MMP) activity and both MMP and IL-1 synthesis. The aim of this study was to evaluate the role of doxycycline as an inhibitor of corneal MMPs and assess its contribution to ocular surface repair mechanisms. Methods: Corneal epithelial cell and keratocyte cultures were grown to confluence and incubated with IL-1α, LPS, doxycycline, or doxycycline and LPS in serum free medium for 4 days. The cells were either harvested and assayed for caspase-3 activity or stained with either AE5 or antivimentin antibodies. Media samples were concentrated and assayed for MMP activity by zymography or using a fluorigenic substrate. ELISA was used to quantify IL-1α, MMPs -1,-2,-3,-9, and TIMPs -1 and -2. Results: IL-1α and LPS had no effect on MMP/TIMP production by cultured corneal epithelial cells and keratocytes. Corneal MMP-2 inhibition by doxycycline was partially [Ca2+] dependent but irreversible. At the minimum inhibitory concentration, 100 μm, doxycycline had no apparent effect on MMP and TIMP production, but ultimately caused the death of keratocytes and some of the epithelial cells that detached from their basement membrane. Caspase-3 activity was not detected in dead or dying keratocytes. The mechanism of cell death in cultured corneal epithelial cells was not caspase-3 related apoptosis as the activity of this enzyme, normally detectable, was lost. The epithelial cells that survived doxycycline treatment did not bind antivimentin antibody and compared with controls, reacted less with the AE5 antibody. They were probably transient amplifying cells. Conclusions: Doxycycline irreversibly inhibits corneal MMP-2 activity by chelating the metal ions that are catalytically and structurally essential. Corneal MMP/TIMP production in vitro is not modulated by IL-1α, LPS, or doxycycline. The therapeutic value of doxycycline may depend upon its effective concentration at the ocular surface and probably relates to its chelating properties.

Background/aim: A current consensus in epidemiological studies of primary angle closure (PAC) is to diagnose the condition only if the posterior ( usually pigmented) trabecular meshwork is seen for less than 90degrees of the angle circumference, termed an "occludable angle.'' The authors sought to assess the validity of this epidemiological classification by exploring the relation between drainage angle width, peripheral anterior synechiae ( PAS) and glaucomatous optic neuropathy (GON).Methods: 918 Mongolians and 995 Chinese Singaporeans, both groups aged 40 years and older were examined in two population based surveys. Gonioscopic angle width was graded in five categories ( 0 = closed to 4 = wide open) according the scheme described by Shaffer. Cases with secondary PAS were excluded.Results: The rate of PAS was between 0.3% and 1.7% in people with wide angles ( grades 3 and 4). In those with grade 2 angles, PAS were seen in between 8% of eyes. In eyes with grade 1 angles, the rate rose to 17% in Chinese Singaporeans, and 31% in Mongolians. The odds of PAS were higher in people with narrower angles. However, there was a greater absolute number of people with PAS whose drainage angles were classified as "not occludable'' than those classified "occludable.''Conclusions: The traditional view that primary angle closure becomes a significant possibility in drainage angles of less than or equal to grade 2 (approximately 20degrees) is valid in east Asians. The definition of an "occludable'' angle examined here excludes many people with PAS. This probably serves to underemphasise the role of PAC in population surveys of glaucoma prevalence in Asian people.

To evaluate the risk factors for rubeosis iridis by colour Doppler imaging (CDI) in patients with complete internal carotid artery occlusion (ICAO).34 eyes of 32 consecutive patients with complete ICAO were enrolled. Using CDI, blood flow direction (forward, reverse, undetectable) in the ophthalmic artery (OA), central retinal artery (CRA), and short posterior ciliary artery (SPCA) were determined. Arterial mean blood velocity (Vmean) and resistive index (RI) were calculated and correlations between the rubeosis iridis incidence and CDI parameters analysed.The eyes were classified into four types according to blood flow direction: forward flow in OA, CRA, and SPCA (type 1; n = 11); reverse OA and forward CRA and SPCA flow (type 2a; n = 12); reverse OA and undetectable CRA and SPCA flow (type 2b; n = 8); undetectable flow in all three arteries (type 3; n = 3). Rubeosis iridis was seen only in type 2b and 3 eyes. Type 2b showed significantly (p0.01) higher Vmean and lower RI values in the OA, indicating more rapid reverse flow than in type 2a eyes. Although in type 1 and 2a eyes OA flow was in opposite directions, they manifested no rubeosis iridis and no difference in the Vmean and RI values of the CRA and SPCA.The classification of eyes from patients with ICAO into four types by CDI may facilitate the identification of the eyes at high risk for rubeosis iridis. Markedly diminished flow in both the CRA and SPCA may result in rubeosis iridis, regardless of OA flow direction.

Background/aims: To compare the relative risks of poly (methylmethacrylate) (PMMA) and soft acrylic (AcrySof) primary intraocular lens (IOL) implantation in paediatric cataract surgery. Methods: A retrospective analysis of clinical data was performed on eyes of 61 infants and children who underwent cataract surgery with primary IOL implantation. Age at operation ranged from 3 weeks to 15 years. Mean follow up duration was 24.5 months (range 0.5–68 months). Factors examined included type of IOL (PMMA, acrylic), performance of a primary posterior continuous curvilinear capsulorhexis (PCCC) or capsulotomy with limited anterior vitrectomy, perioperative complications, and subsequent intervention for posterior capsule opacification (PCO). Risk factors for perioperative complications were examined with 2×2 tables to give odds ratios (OR) as measures of association. A survival analysis was performed to assess risk of subsequent intervention for PCO with different IOL types. Relative risks (hazards) and confidence intervals (CI) were calculated with Cox regression to adjust for potential confounding. Results: Compared to acrylic, PMMA IOLs were significantly associated with perioperative complications (OR 5.2, 95% CI 1.4 to 19, p = 0.01). However, IOL and type of section were highly correlated factors, and this finding may reflect risks associated with larger scleral wounds used for PMMA IOLs. No statistically significant difference in risk of subsequent intervention for PCO was found between different IOL types. Mean times till intervention for PMMA and acrylic IOLs were 30.1 months (95% CI 22 to 38) and 19.8 months (95% CI 12 to 27) respectively (log rank test statistic 1.53, one degree of freedom, p = 0.22). At 12 months post-implant surgery, 76% (95% CI 59 to 93) of PMMA cases and 54% (95% CI 35 to 72) of acrylic cases had not required intervention for PCO; these proportions fell to 55% (95% CI 35 to 75) and 38% (95% CI 14 to 61) for PMMA and acrylic cases respectively at 2 years post-surgery. After adjustment for age at surgery, primary posterior capsulorhexis, and perioperative complications relative risk of intervention after acrylic IOL implantation was 1.6 (95% CI 0.66 to 3.9, p = 0.29). Conclusion: Primary implantation of foldable soft acrylic IOLs in paediatric eyes may allow fewer perioperative complications than rigid PMMA IOLs. Short term safety profiles of primary implantation in paediatric cataract surgery are otherwise comparable for PMMA and soft acrylic IOLs.

Aims: To evaluate whether determination of the central retinal artery and vein collapse pressure correlate with systemic blood pressure measurements, using a new Goldmann contact lens associated ophthalmodynamometric device Methods: The prospective clinical study included 92 eyes of 92 patients presenting with cataract or refractive problems (n = 40; control study group) or with retinal and orbital pathologies (n = 52). With topical anaesthesia, a Goldmann contact lens fitted with a pressure sensor in its holding ring was placed onto the cornea. Pressure was asserted onto the globe by pressing the contact lens, and the pressure value at the time when the central retinal artery and vein started pulsating were noted as central retinal artery and vein collapse pressure. Additionally, the brachial arterial blood pressure was measured. Results: In the control study group, central retinal artery collapse pressure was highly significantly correlated with diastolic blood pressure (correlation coefficient r = 0.77; p r = 0.35; p = 0.03). Central retinal vein collapse pressure was statistically independent of diastolic blood pressure (p = 0.11). In eyes with retinal or orbital diseases, the correlation coefficients were lower than in the control study group. In eyes with retinal arterial occlusions, central retinal vessel collapse pressure measurements were not correlated with arterial blood pressure measurements. Conclusions: Depending on coexisting retinal or orbital diseases, ophthalmodynamometric estimation of the central retinal artery collapse pressure, performed during a routine Goldmann contact lens ophthalmoscopy, correlates with systemic blood pressure measurements.