Background
Certificate of Vision Impairment (CVI) is used to register patients as sight impaired (SI) or severely sight impaired (SSI), based on visual function. CVI mobilises social services and provides epidemiological data. However, many eligible patients remain unregistered, or are registered incorrectly, ‘missing out’ on benefits to which they are entitled.

 

Aims
To determine whether patients at University Hospital Birmingham (UHB) are correctly registered according to guidelines;To evaluate the accuracy of completion of CVI forms, as compared to clinical data in medical records;To investigate delays in CVI registration and assess reasons for these (e.g. social deprivation, ethnicity, ophthalmic diagnosis).

 

Methods
Patients registered SI/SSI at UHB (1/1/13 – 31/7/13) were identified. Residence postcode was utilised to determine social deprivation scores by Index of Multiple Deprivation 2007, with division into quintiles (quintile 1: least deprived, quintile 5: most deprived). Statistical analysis was with Mann-Whitney (2 groups) and Kruskal-Wallis tests (>2 groups).

 

Results
Of 125 patients, 70% were registered SI. Median age 82 years, 66% female, 86% White. Overall, 18% were incorrectly registered. Of correct registrations, 50% were delayed (median 12 months). Greater delays existed in ethnic minority (White, 48% vs Non-White, 64%) and deprived (quintile 1, 17% vs quintile 5, 21%) patients. [50]

 

Conclusion
In this single-centre study, a significant proportion of patients were incorrectly registered, with substantial delay. Delays were disproportionately represented in groups in greatest need of support. Future studies should investigate further the association between ethnicity, deprivation and access to CVI.

Background
Proliferative vitreoretinopathy (PVR) is the main blinding complication of retinal detachment surgery, occurring in around 5% of patients. PVR is associated with vitreal migration, activation and proliferation of retinal pigment epithelial cells influenced by paracrine cytokines. Transforming growth factor-beta (TGF-β) is an important pro-fibrotic ocular cytokine, opposed by decorin.

 

Aims
To investigate the relationship between vitreous levels of TGF-beta and decorin and the development of PVR.

 

Methods
A prospective observational cohort study was conducted recruiting patients undergoing vitrectomy for retinal detachment, macular holes and established PVR. Vitreous, collected at the start of vitrectomy was analysed by enzyme-linked immunosorbent assay to measure TGF-β and decorin levels and results compared to clinical outcome data.

 

Results
1) TGF-β levels were higher and decorin levels were lower in patients with retinal detachment who went on to develop PVR. 2) Patients with macular holes had lower levels of both decorin and TGF-beta. 3) Patients with established PVR had the highest levels of both TGF-β and decorin.

 

Conclusion
We hypothesise that TGF-β release occurs in response to retinal detachment, driving a pro-fibrotic response and causing PVR. Decorin is released as an anti-fibrotic regulatory mechanism, initial failure of which increases PVR risk, suggesting that decorin supplementation at the time of vitrectomy could reduce the subsequent risk of PVR.

Background
There is little understanding of the effect of idiopathic intracranial hypertension (IIH) on quality of life (QOL) and additionally which factors contribute to quality of life in IIH patients.

 

Methods
QOL was assessed using the 36-Item Short Form Health Survey before and after a therapeutic dietary intervention which resulted in significant reduction in body mass index (BMI), intracranial pressure (ICP), papilloedema (optical coherence tomography measure of retinal nerve fibre layer), acuity (Logarithm of the Minimal Angle of Resolution), perimetric mean deviation (Humphrey 24-2) and headache (six-item headache impact test (HIT-6) and diary evaluation of severity). Baseline QOL was compared to an age and gender matched population. We then evaluated the relationship between the above clinical outcomes to changes in QOL.

 

Results
At baseline, QOL domains were significantly lower in IIH compared to an age and gender matched population, p< 0.001. Therapeutic weight loss led to a significant improvement in 8 out of 11 QOL domains in conjunction with the previously published data demonstrating significant improvement in papilloedema, visual acuity, perimetry and headache, p < 0.001. Improving QOL domains correlated significantly with headache recovery (p < 0.001). However, despite significant improvement in the other clinical measures they did not correlate with improving QOL domains.

 

Conclusion
We demonstrate a significantly reduced QOL in IIH patients. QOL improved with therapeutic weight loss alongside significant improvement in ICP, papilloedema, acuity, perimetry and headache. However, headache was the only clinical outcome that correlated with enhanced QOL. We suggest that effective headache management is required to improve QOL in IIH.

Aim
To evaluate the patient profile and management of those seen in the lupus and hydroxychloroquine clinic at the Queen Elizabeth Hospital.

 

Abstract
Hydroxychloroquine is an anti-malarial drug that can be used in the treatment of systemic lupus erythematosis (SLE) and other rheumatological diseases. Whilst it is generally well tolerated, one of its known but rare side effects is retinal toxicity and retinopathy.  The SLE and hydroxychloroquine (HCQ) clinic at the Queen Elizabeth Hospital offers exceptional access to a large body of patients taking hydroxychloroquine.  This study aims to review the patient profile and management of the 204 patients referred to the clinic, looking at the investigations performed and management particularly of 2 with definite HCQ toxicity and a further 2 with probable disease resulting in their HCQ being stopped.  The data provided should give a valuable insight into the intricacies of monitoring and management of these patients in clinic.

Purpose
Polymerase chain reaction (PCR) is increasingly important for the rapid detection of fungal keratitis. However, techniques of specimen collection and DNA extraction before PCR may interfere with test sensitivity. The purpose of this study was to investigate the use of DNA-stabilizing FTA filter paper (Indicating FTA filter paper; Whatman International, Ltd., Maidstone, UK) for specimen collection without DNA extraction in a single-step, non-nested PCR for fungal keratitis. 

 

Methods
Specimens were collected from ocular surfaces with FTA filter discs, which automatically lyse collected cells and stabilize nucleic acids. Filter discs were directly used in single-step PCR reactions to detect fungal DNA. Test sensitivity was evaluated with serial dilutions of Candida albicans, Fusarium oxysporum, and Aspergillus fumigatus cultures. Test specificity was analyzed by comparing 196 and 155 healthy individuals from Switzerland and Egypt, respectively, with 15 patients with a diagnosis of microbial keratitis. 

 

Results
PCR with filter discs detected 3 C. albicans, 25 F. oxysporum, and 125 A. fumigatus organisms. In healthy volunteers, fungal PCR was positive in 1.0% and 8.4% of eyes from Switzerland and Egypt, respectively. Fungal PCR remained negative in 10 cases of culture-proven bacterial keratitis, became positive in 4 cases of fungal keratitis, but missed 1 case of culture-proven A. fumigatus keratitis. 

 

Conclusion
FTA filter paper for specimen collection together with direct PCR is a promising method of detecting fungal keratitis. The analytical sensitivity is high without the need for a semi-nested or nested second PCR, the clinical specificity is 91.7% to 99.0%, and the method is rapid and inexpensive.

Background
Graves’ disease (GD) as an immune reconstitution inflammatory syndrome (IRIS) following highly active antiretroviral therapy (HAART) for human immunodeficiency virus (HIV) has previously been reported. However, clinical challenges associated with HIV in the context of ophthalmic manifestations of GD, namely Thyroid Eye Disease (TED), are not as well-characterised. 

 

Aims
We aimed to determine the prevalence of HIV-TED co-pathology in our unit, to describe TED presentation and course in the context of HIV, to evaluate management difficulties peculiar to TED in those with HIV infection, and how these may be overcome.  

 

Methods
Cross-sectional study of all patients with co-existence of GD and HIV infection at University Hospital Birmingham (2003 – 2014). Retrospective case note review to identify TED with particular reference to HAART regimen, CD4+ T cell count, HIV viral load and TED activity and severity.  

 

Results
Of 783 GD and 1186 HIV patients, only 11 had HIV-GD and 3 HIV-TED. Each was of Afro-Caribbean origin, in their fourth decade, and presented with undetectable CD4+ T cells and high HIV viral load. Each developed GD >3 years following HAART and each had severe TED requiring surgical intervention.

 

Conclusion
TED in the context of HIV is uncommon, but may represent a sub-group predisposed to severe orbitopathy. Many challenges exist, including safe immunosuppression, and HAART drug interactions with anti-thyroid drugs. To better understand TED in HIV, and to counsel patients with this co-pathology most effectively, future multi-centre surveillance is required.

Background
Unifying terminology is vital for standardising disease descriptions, determining treatment responses, and ensuring robust outcomes for research trials. Clinical indices may be categorised into (i) activity: reversible manifestations or (ii) damage: manifestations that are persistent and result from previously active disease.

 

Aims
The purpose of this study was to obtain consensus on core domains for the assessment of disease activity/damage in the context of ultimately defining an agreed ocular surface disease (OSD) scoring system. 

 

Methods
An anonymized online-questionnaire was distributed to an international group of specialists. Recipients were asked to rank 76 indices. A >75% consensus was required for inclusion/exclusion. Equivocal responses were electronically and anonymously arbitrated by a pre-determined OSD Expert Steering Group, who also considered measures of ‘activity’ or ‘damage’ for each index.  

 

Results
53 experts (40 OSD, 8 uveitis, 5 oculoplastics) from 8 countries defined 75% agreement for the inclusion of 52/76 clinical parameters with a further 15 equivocal/novel indices included following Steering Group arbitration. The final list of indices and tools comprised 3 tear-film (4 tools), 21 eyelid (3), 17 conjunctiva(3), 15 cornea(10) and 11 sclera/anterior chamber(2). Of these 14 were considered as measures of activity, 25 as damage and 50 as measures of both. 

 

Conclusion
This is the first international consensus on putative descriptors of OSD and discriminators of disease activity and damage. The consensus affords a platform for the development of scoring systems for OSD, extracted datasets for electronic patient records, and development of objective tools such as fornix depth measurers for assessment of OSD.

Background
Haemopoietic Stem Cell Transplant (HSCT) has revolutionised the treatment of haematological disease, offering a potential cure for previously fatal conditions. Graft-versus-Host disease (GVHD) remains the major complication of HSCT. Ocular complications of GVHD, such as dry eye, remain common, occurring in over 80%.

 

Aims
Our aim was to describe the conjunctival immune environment longitudinally before and after HSCT as the transplanted immune system reconstitutes over the course of one year. Secondly we aimed to investigate any differences in the conjunctival leukocyte population in patients with and without GVHD related dry eye disease. 

 

Methods
Six patients were seen before HSCT and at 1, 3, 6 and 12 months post-HSCT. A second cohort of 23 patients (100 days post-HSCT) and six controls were recruited. Schirmer’s test and conjunctival impression cytology were performed. Cells were stained with fluorochrome-labelled antibodies and flow cytometry performed. 

 

Results
Conjunctival lymphocyte numbers dropped post-HSCT. At six months, CD8 lymphocytes normalised, whilst CD4 lymphocytes remained significantly higher. In the 100 day post-HSCT cohort, the conjunctiva of dry eyes (9/46 eyes, five patients) contained more neutrophils (p=0.002) and monocytes (p=0.001) than eyes with Schirmer’s >=6mm. 

 

Conclusion
Post-HSCT, the resident conjunctival lymphocyte population declines rapidly, with reconstitution taking 6 months. A subsequent elevation in CD4 lymphocytes may indicate abnormal conjunctival immune reconstitution, which may predispose to subsequent inflammation. In dry eyes there was evidence of inflammation, notably raised neutrophils and monocytes, justifying anti-inflammatory treatment.

Background
Of the TGFβ isoforms, TGFβ2 is found at highest levels in the aqueous humour, and is thought to control local T cell responses with particular significance in uveitis. Betaglycan is a component of the TGFβ receptor considered necessary for TGFβ2 signalling, although its role in T cell biology is unknown.

 

Aims
To develop an experimental model in which to study the effect of betaglycan deficiency on immune regulation, with particular emphasis on TGFβ signalling to T cells. This presentation specifically seeks to highlight the importance of basic (non-ophthalmic) science to ophthalmologists, discussing translation of laboratory findings to clinical practice.

 

Methods
Since complete betaglycan deficiency is embryonic lethal, we generated mixed foetal liver stem cell chimeras where deficiency was restricted only to T and B cells. After assessing gross phenotype, TGFβ-dependent T cell responses were investigated both through in-vivo controlled antigenic challenge and in-vitro naïve T cell differentiation assays.

 

Results
We successfully developed a novel animal model of betaglycan deficiency; animals were viable and displayed no gross phenotypic abnormalities. Betaglycan-deficient animals showed no evidence of disordered immune regulation in response to in-vivo controlled antigenic challenge by several routes. TGFβ2-dependent differentiation of naïve T cells in-vitro was unaffected by betaglycan deficiency. 

 

Conclusion
We have used a non-ophthalmic model to address an ophthalmic research question. Whilst we have been unable to confirm a role for betaglycan in uveitis pathogenesis, we have increased understanding of TGFβ signalling to T cells. Basic science allows experimental manipulation of real-life systems and remains crucially important to ophthalmologists.

Background
Descemet stripping automated endothelial keratoplasty (DSAEK) is widely performed as the procedure of choice for corneal decompensation secondary to endothelial dysfunction. There are increasing reports in the literature of intraocular lens (IOL) opacification as an emerging late post-operative complication of DSAEK.

 

Aims
To identify cases of IOL opacification after DSAEK from our practice and describe potential aetiological factors.

 

Methods
In this retrospective, non-comparative case series, pseudophakic patients diagnosed with IOL opacification after DSAEK between January 2010 and April 2014 were identified from corneal clinic records. Notes were reviewed for demographic data, diagnosis, details of cataract surgery including IOL model, peri-operative details of DSAEK and post-operative course.

 

Results
Six cases of central, crystalline IOL opacification were identified. Mean age was 75.6 years. All patients had hydrophilic acrylic IOL models. Five patients (83%) required early post-operative graft re-bubbling for partial graft dislocation, and one had significantly elevated IOP. Five cases have been managed conservatively and one IOL exchange has been undertaken.  

 

Conclusion
Post-DSAEK IOL opacification was exclusively associated with hydrophilic acrylic IOL models. Repeated exposure to intracameral air/gas, e.g. after graft re-bubbling, may be a major aetiological factor, although raised IOP and other patient factors may contribute. Hydrophilic acrylic IOLs should be avoided in patients at risk of developing corneal decompensation.

Background
In the United Kingdom there is opportunistic screening for glaucoma at the optometrists. Introduction of national guidelines have increased glaucoma suspects being directed to the hospital eye services. High false positive (40-50%) rates have led to capacity issues and patient safety concerns with delays in diagnosis of those with disease.

 

Aims
To review the impact of local glaucoma referral refinement on the service demand, referral quality and patient outcomes at a district general hospital.

 

Methods
Consecutive referrals (n=100) were reviewed in April 2012 and repeated in April 2013 after refinement. The refinement scheme entailed repeat intraocular pressure test with applanation and/or a repeat visual field test by the optometrists. Hospital one-stop glaucoma clinics were established and data recorded on the electronic patient record system.

 

Results
Referrals averaged 90/month (range 77-126, SD±17.9). Referrals for raised pressures reduced from 37% to 28%. Referrals with field and disc abnormalities increased from 29% and 44% to 37% and 57%. A greater proportion required treatment in 2013 (p=0.27). There was no change in false positive referrals (44% versus 41%, p=0.42).  

 

Conclusion
Glaucoma referral refinement demonstrated by QIPP study was not replicated in our region. A quarter of referrals needed management at secondary-care level. Refinement at one-stop glaucoma clinics to establish diagnosis and further management in primary-care using commissioning guidance may provide a more efficient option alongside maintenance of a Glaucoma Register.

Aims
To describe the prevalence and natural history of retinopathy in a cohort of children and young people with Type 1 diabetes attending a tertiary hospital diabetes clinic.

 

Methods
We analysed follow-up data from 2008 to 2010 on all children eligible for retinopathy screening using the ‘Twinkle’ diabetes database and the regional retinal screening database.

 

Results
88% (149/169) of eligible children were screened in 2008, median age 14 years, 52% male. The prevalence of retinopathy was 19.5% (30/149) (all background retinopathy grade R1). There was significant difference in median (range) duration of diabetes, 7.7 years (0.6-13.7) vs. 5 years (0.2-12.5) (p< 0.001) and median (range) HbA1C, 9.1% (7.2-14) vs. 8.6% (5.6-13.1) (p=0.02), between the groups with and without retinopathy. At 2 years follow-up, 12/30 (40%) had unchanged retinopathy grade R1, 10/30 (33.3%) showed resolution of changes (R0), 1/30 progressed to maculopathy, and 7/30 had no follow-up data. Median (range) HbA1C in 2008 and 2010 for the groups with stable vs. resolved changes was similar, 9.1% (7.2-14) and 9.2% (7-14) vs. 9.5%(7.8-14) and 9.2%(8.7-14). Of the 119 without retinopathy in 2008, 27 (22.5%) had developed retinopathy within 2 years, including 1 with pre proliferative retinopathy and 1 with maculopathy. There were no significant differences in HbA1c between those who progressed to retinopathy and those who did not, 8.7% (7.1-13.1) vs. 8.6% ( 6.3-12.2).  

 

Conclusion
The prevalence of background retinopathy in our cohort was comparable to previously published reports, with higher HbA1c and longer duration of diabetes being significant risk factors. On short term follow up, Grade 1 retinopathy is likely to resolve in a third of patients and remain unchanged in just over a third.

Background
Traumatic optic neuropathy is associated with irreversible visual loss and there are no clinically effective treatments. The mTOR cellular signalling pathway is implicated as a determinant of neuronal viability and regenerative ability after CNS injury. Modulation of mTOR signalling may offer novel therapeutic targets for development of translatable sight-saving therapies.

 

Aims
To determine whether modulation of mTOR signalling, through small interfering RNA (siRNA)-mediated knock-down of the negative regulator RTP801, promotes retinal ganglion cell (RGC) neuroprotection and axon regeneration in a model of traumatic optic neuropathy.

 

Methods
Anaesthetised adult rats underwent bilateral optic nerve crush (ONC), followed by intravitreal delivery of siRNA targeting RTP801 (siRTP801) to one eye and control (siEGFP) to the fellow eye, 0d, 8d, and 16d after ONC. RGC survival and axon regeneration were evaluated after 24d by immunohistochemistry of retinal and optic nerve sections.

 

Results
Intravitreal siRTP801 was RGC neuroprotective after ONC, with 82% RGC survival at 24d, compared to 45% in controls (p< 0.001). Significantly increased axon regeneration was observed up to 1200μm beyond the injury site, associated with a potentiated response from activated retinal astrocytes and Müller glia.  

 

Conclusion
SiRNA-mediated knock-down of the mTOR negative regulator RTP801 promotes significant RGC neuroprotection and axon regeneration after optic nerve injury, associated with modulation of the retinal glial response. Manipulation of mTOR cellular signalling may contribute to the development of novel translatable therapies to restore vision after traumatic optic neuropathy.

Background
Graves’ disease (GD) as an immune reconstitution inflammatory syndrome (IRIS) following highly active antiretroviral therapy (HAART) for human immunodeficiency virus (HIV) has previously been reported. However, clinical challenges associated with HIV in the context of ophthalmic manifestations of GD, namely Thyroid Eye Disease (TED), are not as well-characterised.

 

Aims
We aimed to determine the prevalence of HIV-TED co-pathology in our unit, to describe TED presentation and course in the context of HIV, to evaluate management difficulties peculiar to TED in those with HIV infection, and how these may be overcome.

 

Methods
Cross-sectional study of all patients with coexistence of GD and HIV infection at University Hospital Birmingham (2003 – 2014). Retrospective case note review to identify TED with particular reference to HAART regimen, CD4+ T cell count, HIV viral load and TED activity and severity.

 

Results
Of 783 GD and 1186 HIV patients, only 11 had HIV-GD and 3 HIV-TED. Each was of Afro-Caribbean origin, in their fourth decade, and presented with undetectable CD4+ T cells and high HIV viral load. Each developed GD >3 years following HAART and each had severe TED requiring surgical intervention.

 

Conclusion
TED in the context of HIV is uncommon, but may represent a sub-group predisposed to severe orbitopathy. Many challenges exist, including safe immunosuppression, and HAART drug interactions with anti-thyroid drugs. To better understand TED in HIV, and to counsel patients with this co-pathology most effectively, future multi-centre surveillance is required.

Background
There is little understanding of the effect of idiopathic intracranial hypertension (IIH) on quality of life (QOL) and additionally which factors contribute to quality of life in IIH patients.

 

Aims
We aimed to determine the prevalence of HIV-TED co-pathology in our unit, to describe TED presentation and course in the context of HIV, to evaluate management difficulties peculiar to TED in those with HIV infection, and how these may be overcome.

 

Methods
QOL was assessed using the 36-Item Short Form Health Survey before and after a therapeutic dietary intervention which resulted in significant reduction in body mass index (BMI), intracranial pressure (ICP), papilloedema (optical coherence tomography measure of retinal nerve fibre layer), acuity (Logarithm of the Minimal Angle of Resolution), perimetric mean deviation (Humphrey 24-2) and headache (six-item headache impact test (HIT-6) and diary evaluation of severity). Baseline QOL was compared to an age and gender matched population. We then evaluated the relationship between the above clinical outcomes to changes in QOL.

 

Results
At baseline, QOL domains were significantly lower in IIH compared to an age and gender matched population, p< 0.001. Therapeutic weight loss led to a significant improvement in 8 out of 11 QOL domains in conjunction with the previously published data demonstrating significant improvement in papilloedema, visual acuity, perimetry and headache, p< 0.001. Improving QOL domains correlated significantly with headache recovery (p< 0.001). However, despite significant improvement in the other clinical measures they did not correlate with improving QOL domains. 

 

Conclusion
We demonstrate a significantly reduced QOL in IIH patients. QOL improved with therapeutic weight loss alongside significant improvement in ICP, papilloedema, acuity, perimetry and headache. However, headache was the only clinical outcome that correlated with enhanced QOL. We suggest that effective headache management is required to improve QOL in IIH.

Introduction
Referral of glaucoma suspects from optometrists increased significantly since the launch of NICE guidance. This has led to an increase in false positives referred which burdens the glaucoma service. In a recent audit of our service half of the patients who have been referred with glaucoma by their opticians were discharged in the same visit. That led us to try to improve our practice by initiating our glaucoma referral refinement scheme where we trained strategically placed optometrists to become community optometrists with specialist interest in glaucoma (COSIG). All optometrist referrals were screened by a COSIG, who decided on referral it to an eye specialist (ES) , in the hope this would increase the positive predictive value of referrals.

 

Methods
Retrospective study of our first fifty consecutive patients referred by COSIG. Data collected from COSIG referral letters were compared to ES findings. Data collected included intraocular pressure, cup to disc ratio, gonioscopy grading and any other glaucomatous sign picked by COSIG.

 

Analysis
36 patients (73%) had an active management, an increase of over 20% from our previous study, including 9 patients diagnosed with primary open angle glaucoma, 6 patients with ocular hypertension, 6 patients diagnosed with narrow angle glaucoma, 3 with pigment dispersion syndrome and 12 patients deemed to be glaucoma suspects and kept under active monitoring.

 

Discussion
Our glaucoma refinement scheme certainly improved the referral quality by opticians leading to a more efficient and effective use of resources and the patients in greatest demand being assessed in the clinic with less delay. With us actively teaching the COSIGs to further improve their clinical knowledge this will hopefully lead to an even higher true positive referral in a future re-audit.