Relationships between retinal layer thickness and brain volumes in the UK Biobank cohort.

BACKGROUND AND PURPOSE: Current methods to diagnose neurodegenerative diseases are costly and invasive. Retinal neuroanatomy may be a biomarker for more neurodegenerative processes and can be quantified in vivo using optical coherence tomography (OCT), which is inexpensive and noninvasive. We examined the association of neuroretinal morphology with brain MRI image-derived phenotypes (IDPs) in a large cohort of healthy older people. METHODS: UK Biobank participants aged 40 to 69 years old underwent comprehensive examinations including ophthalmic and brain imaging assessments. Macular retinal nerve fibre layer (mRNFL), macular ganglion cell-inner plexiform layer (mGCIPL), macular ganglion cell complex (mGCC) and total macular thicknesses were obtained from OCT. Magnetic resonance imaging (MRI) IDPs assessed included total brain, grey matter, white matter and hippocampal volume. Multivariable linear regression models were used to evaluate associations between retinal layers thickness and brain MRI IDPs, adjusting for demographic factors and vascular risk factors. RESULTS: A total of 2131 participants (mean age 55 years; 51% women) with both gradable OCT images and brain imaging assessments were included. In multivariable regression analysis, thinner mGCIPL, mGCC and total macular thickness were all significantly associated with smaller total brain (p < 0.001), grey matter and white matter volume (p < 0.01), and grey matter volume in the occipital pole (p < 0.05). Thinner mGCC and total macular thicknesses were associated with smaller hippocampal volume (p < 0.02). No association was found between mRNFL and the MRI IDPs. CONCLUSIONS: Markers of retinal neurodegeneration are associated with smaller brain volumes. Our findings suggest that retinal structure may be a biomarker providing information about important brain structure in healthy older adults.

Latanoprost for open-angle glaucoma (UKGTS): a randomised, multicentre, placebo-controlled trial.

BACKGROUND: Treatments for open-angle glaucoma aim to prevent vision loss through lowering of intraocular pressure, but to our knowledge no placebo-controlled trials have assessed visual function preservation, and the observation periods of previous (unmasked) trials have typically been at least 5 years. We assessed vision preservation in patients given latanoprost compared with those given placebo. METHODS: In this randomised, triple-masked, placebo-controlled trial, we enrolled patients with newly diagnosed open-angle glaucoma at ten UK centres (tertiary referral centres, teaching hospitals, and district general hospitals). Eligible patients were randomly allocated (1:1) with a website-generated randomisation schedule, stratified by centre and with a permuted block design, to receive either latanoprost 0·005% (intervention group) or placebo (control group) eye drops. Drops were administered from identical bottles, once a day, to both eyes. The primary outcome was time to visual field deterioration within 24 months. Analyses were done in all individuals with follow-up data. The Data and Safety Monitoring Committee (DSMC) recommended stopping the trial on Jan 6, 2011 (last patient visit July, 2011), after an interim analysis, and suggested a change in primary outcome from the difference in proportions of patients with incident progression between groups to time to visual field deterioration within 24 months. This trial is registered, number ISRCTN96423140. FINDINGS: We enrolled 516 individuals between Dec 1, 2006, and March 16, 2010. Baseline mean intraocular pressure was 19·6 mm Hg (SD 4·6) in 258 patients in the latanoprost group and 20·1 mm Hg (4·8) in 258 controls. At 24 months, mean reduction in intraocular pressure was 3·8 mm Hg (4·0) in 231 patients assessed in the latanoprost group and 0·9 mm Hg (3·8) in 230 patients assessed in the placebo group. Visual field preservation was significantly longer in the latanoprost group than in the placebo group: adjusted hazard ratio (HR) 0·44 (95% CI 0·28-0·69; p=0·0003). We noted 18 serious adverse events, none attributable to the study drug. INTERPRETATION: This is the first randomised placebo-controlled trial to show preservation of the visual field with an intraocular-pressure-lowering drug in patients with open-angle glaucoma. The study design enabled significant differences in vision to be assessed in a relatively short observation period. FUNDING: Pfizer, UK National Institute for Health Research Biomedical Research Centre.

Advanced cocaine-related necrotising sinusitis presenting with restrictive ophthalmolplegia.

We report a case of bilateral infero-medial orbital wall destruction, associated with loss of sinonasal architecture. The patient presented with intermittent horizontal diplopia following an acute on chronic infective sinusitis. Eight months previously the patient had developed a midline hard palate fistula for which a palatine prosthesis had been fitted. The broad differential diagnosis is discussed, though in this patient chronic cocaine abuse was identified as the underlying aetiology. Eye movement restriction worsened progressively with bilateral inflammation around the medial and inferior rectus muscles. Attempts to resolve the recurring cycle of sinus infection and inflammation by palatal fistula closure failed despite augmented techniques mobilising flaps from both nasal and palatal sides.

Type 2 diabetes mellitus and microvascular complications 1 year after Roux-en-Y gastric bypass: a case-control study.

AIMS/HYPOTHESIS: We aimed to examine the effects of bariatric surgery on microvascular complications in patients with type 2 diabetes using objective measures. METHODS: Prospective case-control study of 70 obese surgical patients with type 2 diabetes undergoing gastric bypass surgery matched for age, sex and duration of diabetes to 25 medical patients treated using international guidelines. Microvascular complications were assessed before and 12-18 months after intervention using urine albumin creatinine ratio (ACR) measurements, two-field digital retinal images and peripheral nerve conduction studies (in the surgical group only). RESULTS: Urine ACR decreased significantly in the surgical group but increased in the medical group. There were no significant differences between the surgical and medical groups in the changes in retinopathy. There were no changes in the nerve conduction variables in the surgical group. CONCLUSIONS/INTERPRETATION: In the short term, bariatric surgery may be superior to medical care in the treatment of diabetic nephropathy, but not retinopathy or neuropathy.

Resistance to the most common optic neuropathy is associated with systemic mitochondrial efficiency.

Glaucomatous optic neuropathy, an important neurodegenerative condition and the commonest optic neuropathy in humans, is the leading cause of irreversible blindness worldwide. Its prevalence and incidence increase exponentially with ageing and raised intraocular pressure (IOP). Using glaucomatous optic neuropathy as an exemplar for neurodegeneration, this study investigates putative factors imparting resistance to neurodegeneration. Systemic mitochondrial function, oxidative stress and vascular parameters were compared from isolated lymphocytes, whole blood and urine samples between 30 patients who have not developed the neuropathy despite being exposed for many years to very high IOP ('resistant'), 30 fast deteriorating glaucoma patients despite having low IOP ('susceptible'), and 30 age-similar controls. We found that 'resistant' individuals showed significantly higher rates of ADP phosphorylation by mitochondrial respiratory complexes I, II and IV, hyperpolarised mitochondrial membrane potential, higher levels of mitochondrial DNA, and enhanced capacity to deal with cytosolic calcium overload and exogenous oxidative stress, as compared to both controls and glaucoma patients. While it has been known for some years that mitochondrial dysfunction is implicated in neurodegeneration, this study provides a fresh perspective to the field of neurodegeneration by providing, for the first time, evidence that systemic mitochondrial efficiency above normal healthy levels is associated with an enhanced ability to withstand optic nerve injury. These results demonstrate the importance of cellular bioenergetics in glaucomatous disease progression, with potential relevance for other neurodegenerative disorders, and raise the possibility for new therapeutic targets in the field of neurodegeneration.

Recharging mitochondrial batteries in old eyes. Near infra-red increases ATP.

Progressive accumulation of age related mitochondrial DNA mutations reduce ATP production and increase reactive oxygen species output, leading to oxidative stress, inflammation and degradation. The pace of this is linked to metabolic demand. The retina has the greatest metabolic demand and mitochondrial density in the body and displays progressive age related inflammation and marked cell loss. Near infra-red (670 nm) is thought to be absorbed by cytochrome c oxidase (COX), a key element in mitochondrial respiration and it has been demonstrated that it improves mitochondrial membrane potentials in aged eyes. It also significantly reduces the impact of experimental pathology and ameliorates age related retinal inflammation. We show ATP decline with ageing in mouse retina and brain. Also, in these tissues that ATP is significantly increased by 670 nm exposure in old mice. In the retina this was associated with increased COX and reduced acrolein expression. Acrolein, being a free radical marker of retinal oxidative stress, is up regulated in Alzheimer's and retinal degeneration. This is the first demonstration of ATP manipulation in vivo and may provide a simple non-invasive route to combating age related tissue decline.

Peripheral blood mononuclear cell respiratory function is associated with progressive glaucomatous vision loss.

Intraocular pressure (IOP) is currently the only modifiable risk factor for glaucoma and all licensed treatments lower IOP. However, many patients continue to lose vision despite IOP-lowering treatment. Identifying biomarkers for progressive vision loss would have considerable clinical utility. We demonstrate that lower peripheral blood mononuclear cell (PBMC) oxygen consumption rate (OCR) is strongly associated with faster visual field (VF) progression in patients treated by lowering IOP (P < 0.001, 229 eyes of 139 participants), explaining 13% of variance in the rate of progression. In a separate reference cohort of untreated patients with glaucoma (213 eyes of 213 participants), IOP explained 16% of VF progression variance. OCR is lower in patients with glaucoma (n = 168) than in controls (n = 50; P < 0.001) and is lower in patients with low baseline IOP (n = 99) than those with high baseline IOP (n = 69; P < 0.01). PBMC nicotinamide adenine dinucleotide (NAD) levels are lower in patients with glaucoma (n = 29) compared to controls (n = 25; P < 0.001) and strongly associated with OCR (P < 0.001). Our results support PBMC OCR and NAD levels as new biomarkers for progressive glaucoma.

Retinal thinning in Gaucher disease patients and carriers: results of a pilot study.

Both Gaucher disease patients and heterozygous glucocerebrosidase mutation carriers are at increased risk of Parkinson's disease. Retinal thinning has been reported in early Parkinson's disease. Here we used optical coherence tomography to demonstrate thinning of the retinal ganglion cell layer in Gaucher disease patients and carriers who manifest clinical markers of potential early neurodegeneration. Optical coherence tomography may help identify Gaucher disease patients and carriers at increased risk of developing Parkinson's disease.

The United Kingdom Glaucoma Treatment Study: a multicenter, randomized, placebo-controlled clinical trial: design and methodology.

OBJECTIVE: Elevated intraocular pressure (IOP) is a major risk factor for the deterioration of open-angle glaucoma (OAG); medical IOP reduction is the standard treatment, yet no randomized placebo-controlled study of medical IOP reduction has been undertaken previously. The United Kingdom Glaucoma Treatment Study (UKGTS) tests the hypothesis that treatment with a topical prostaglandin analog, compared with placebo, reduces the frequency of visual field (VF) deterioration events in OAG patients by 50% over a 2-year period. DESIGN: The UKGTS is a randomized, double-masked, placebo-controlled, multicenter treatment trial for OAG. PARTICIPANTS: Five hundred sixteen newly diagnosed (previously untreated) patients with OAG were recruited prospectively at 10 centers between 2007 and 2010. METHODS: Patients were assigned by concealed telephone allocation to treatment with a prostaglandin analog (latanoprost 0.005%) or placebo. The observation period was 2 years, with subjects monitored by VF testing, quantitative imaging, optic disc photography, and tonometry at 11 visits. Data were acquired according to novel protocols optimized for the analysis of deterioration velocity. The sample size was determined for a 2-sided error of α=0.05 to detect the difference between 24% and 11% in incident deterioration over a 24-month follow-up at 90% power and assuming a 25% attrition rate. MAIN OUTCOME MEASURES: The primary outcome was time to VF deterioration within 24 months. Secondary outcomes included the deterioration velocity of VF and quantitative imaging measures and the relationship between these velocities and risk factors for deterioration. RESULTS: The study design enabled a short trial with a 2-year observation period and provided data that can be used to assess the feasibility of further shortening trial duration with the progression velocity of VF and structural imaging measurements as outcomes. CONCLUSIONS: The UKGTS is the first randomized, placebo-controlled trial to evaluate the efficacy of medical treatment in reducing VF deterioration in OAG. The measurement of deterioration velocity and inclusion of quantitative imaging has the potential to reduce the number of patients and duration required for subsequent clinical trials. This trial also will quantify risk factors for deterioration, enabling more precise risk profiling of patients and the development of patient management protocols. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

The United Kingdom Glaucoma Treatment Study: a multicenter, randomized, double-masked, placebo-controlled trial: baseline characteristics.

OBJECTIVE: The United Kingdom Glaucoma Treatment Study (UKGTS) tests the hypothesis that treatment with a topical prostaglandin analog, compared with placebo, reduces the frequency of visual field (VF) deterioration events in patients with open-angle glaucoma (OAG) by 50% over a 2-year period. Additional goals are to evaluate study power with novel clinical trial outcomes: (1) VF deterioration velocity and (2) VF and quantitative imaging measurements modeled as joint outcomes. DESIGN: The UKGTS is a randomized, double-masked, placebo-controlled, multicenter treatment trial for OAG. PARTICIPANTS: A total of 516 patients with newly diagnosed (previously untreated) OAG were prospectively recruited at 10 UK centers between 2007 and 2010. METHODS: Eligible patients were randomly assigned to treatment with latanoprost 0.005% or placebo. The observation period was 2 years, with subjects monitored by VF testing, quantitative imaging, optic disc photography, and tonometry at 11 visits. MAIN OUTCOME MEASURES: The primary outcome measure is time to VF deterioration within 24 months. Secondary outcomes include the deterioration velocity of VF and quantitative imaging measures. RESULTS: The main source of referrals was optometrists (88%). A total of 777 subjects were assessed for eligibility, and 261 were excluded because they did not meet the inclusion criteria or declined to participate. The mean age of the 516 participants was 66 years, and 52.9% were male; 90.1% of the participants were white, and approximately one third (32.2%) reported a family history of glaucoma. A total of 777 eyes were eligible at initial assessment. Both eyes were eligible for 265 participants. Mean (standard deviation) intraocular pressure (IOP) at baseline for the eyes with better versus worse mean deviation (MD) was 18.9 (4.1) and 19.9 (4.7) mmHg, respectively (P = 0.0053). Some 56.1% of all eligible eyes had IOP <20 mmHg at baseline. The median (interquartile range) VF MD for all eligible eyes was -2.9 dB (-1.6 to -4.8 dB). CONCLUSIONS: This is the first randomized, placebo-controlled trial to evaluate the efficacy of medical treatment in reducing VF deterioration in OAG. The baseline characteristics for eligible patients and eyes from this cohort are presented and compared with those of previous trials. The baseline characteristics are similar to those of the largely population-based Early Manifest Glaucoma Trial. The early stage of the glaucoma and relatively low IOP at diagnosis suggest remarkably sensitive case findings by community optometrists in the United Kingdom.

Retinal nerve fiber layer thickness and cognitive ability in older people: the Lothian Birth Cohort 1936 study.

BACKGROUND: This study aims to examine the relationship between the retinal nerve fiber layer (RNFL) thickness as measured by optical coherence tomography (OCT) and lifetime cognitive change in healthy older people. METHODS: In a narrow-age sample population from the Lothian Birth Cohort 1936 who were all aged approximately 72 years when tested, participants underwent RNFL measurements using OCT. General linear modeling was used to calculate the effect of RNFL thickness on three domains; general cognitive ability (g-factor), general processing speed (g-speed) and general memory ability (g-memory) using age at time of assessment and gender as co-variates. RESULTS: Of 105 participants, 96 completed OCT scans that were of suitable quality for assessment were analyzed. Using age and gender as covariates, we found only one significant association, between the inferior area RNFL thickness and g-speed (p = 0.049, η2 = 0.045). Interestingly, when we included age 11 IQ as a covariate in addition to age and gender, there were several statistically significant associations (p = 0.029 to 0.048, η2 = 0.00 to 0.059) in a negative direction; decreasing scores on measures of g-factor and g-speed were associated with increasing RNFL thickness (r = -0.229 to -0.243, p < 0.05). No significant associations were found between RNFL thickness and g-memory ability. When we considered the number of years of education as a covariate, we found no significant associations between the RNFL thickness and cognitive scores. CONCLUSIONS: In a community dwelling cohort of healthy older people, increased RNFL thickness appeared to be associated with lower general processing speed and lower general cognitive ability when age 11 IQ scores were included as a covariate.

The Role of Mitophagy in Glaucomatous Neurodegeneration.

This review aims to provide a better understanding of the emerging role of mitophagy in glaucomatous neurodegeneration, which is the primary cause of irreversible blindness worldwide. Increasing evidence from genetic and other experimental studies suggests that mitophagy-related genes are implicated in the pathogenesis of glaucoma in various populations. The association between polymorphisms in these genes and increased risk of glaucoma is presented. Reduction in intraocular pressure (IOP) is currently the only modifiable risk factor for glaucoma, while clinical trials highlight the inadequacy of IOP-lowering therapeutic approaches to prevent sight loss in many glaucoma patients. Mitochondrial dysfunction is thought to increase the susceptibility of retinal ganglion cells (RGCs) to other risk factors and is implicated in glaucomatous degeneration. Mitophagy holds a vital role in mitochondrial quality control processes, and the current review explores the mitophagy-related pathways which may be linked to glaucoma and their therapeutic potential.

Clinical Outcomes and Cost Analysis of PreserFlo versus Trabeculectomy for Glaucoma Management in the United Kingdom.

PURPOSE: Clinical evaluation and cost analysis of mitomycin-C-augmented PreserFlo MicroShunt versus trabeculectomy. DESIGN: Retrospective cohort study across 3 teaching hospitals. PARTICIPANTS: A total of 134 consecutive eyes of 129 patients (70 undergoing MicroShunt, 64 trabeculectomy). METHODS: Primary and secondary glaucoma cases with uncontrolled intraocular pressure (IOP) were included. Neovascular glaucoma and surgery combined with cataract extraction were excluded. The cost analysis used results from the clinical study to estimate operative costs (equipment and staff costs) and postoperative costs (follow-up visits, nonglaucoma medications, and postoperative procedures) per eye for PreserFlo and trabeculectomy. MAIN OUTCOME MEASURES: The primary clinical outcome measure was surgical failure (defined as IOP > 21 mmHg or < 20% reduction from baseline, IOP ≤ 5 mmHg, reoperation, or loss of light perception) or qualified and complete success (with or without medication) at 18 months. Secondary measures were IOP, glaucoma medications, visual acuity, mean deviation, time to cessation of steroid drops, complications, surgical time, follow-up visits, postoperative interventions, and reoperations. The cost analysis evaluated costs of PreserFlo compared with trabeculectomy. RESULTS: Baseline characteristics were similar, except for more non-White patients in the trabeculectomy group (51% Black and Asian vs. 32% MicroShunt, P = 0.02) and more cases with prior ab externo glaucoma surgery in the MicroShunt group (19% vs. 3% in the trabeculectomy group, P = 0.004). Overall, 59% of eyes had primary open-angle glaucoma. Mean follow-up was 19.9 months for both groups. At 18 months, surgical failure was 25% for MicroShunt compared with 35% for trabeculectomy (P = 0.18). Failure in MicroShunt cases was due to inadequate IOP reduction (84%) or reoperation for glaucoma (16%). Failure in trabeculectomy cases was due to inadequate IOP reduction (58%), persistent hypotony (29%), or reoperation for glaucoma (13%). Combined blebitis and endophthalmitis rate was 1.4% for MicroShunt and 3.1% for trabeculectomy. Cost analysis showed a savings of £245 to £566 per eye in the MicroShunt group, driven mostly by reduced postoperative procedures and follow-up visits. This is in contrast to prior randomized controlled trial data reporting the incremental cost of $2058 of PreserFlo over trabeculectomy. CONCLUSIONS: Our experience of introducing PreserFlo MicroShunt surgery showed it was safer than trabeculectomy and is a cost-saving and effective option that offers potential to free up highly limited National Health Service resources. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

One-year surgical outcomes of the PreserFlo MicroShunt in glaucoma: a multicentre analysis.

BACKGROUND/AIMS: To evaluate the efficacy and safety of the PreserFlo MicroShunt glaucoma device in a multicentre cohort study. METHODS: All consecutive patients who received the microshunt with mitomycin-C (MMC) 0.4 mg/mL from May 2019 to September 2020 in three UK tertiary centres. Primary outcome at 1 year was a complete success, with failure defined as intraocular pressure (IOP) >21 mmHg or <20% reduction, IOP≤5 mmHg with any decreased vision on two consecutive visits, reoperation or loss of light perception vision. Secondary outcomes were IOP, best-corrected visual acuity, medications, complications, interventions and reoperations. We also performed subgroup analyses for severe glaucoma and assessed risk factors for failure. RESULTS: 104 eyes had 1-year follow-up. Complete and qualified success at 1 year were achieved in 51.9% (N=54) and 16.4% (N=17), respectively, and failure occurred in 31.7% (N=33). There was a significant reduction in IOP (mmHg) from preoperatively (23.4±0.8, N=104) to 12 months (14.7±0.6, N=104) (p<0.0001). Antiglaucoma medications also decreased from preoperatively (3.4±0.1, N=104) to 12 months (0.7±0.1, N=104) (p<0.0001). Multivariate analyses showed an association between higher mean deviation and failure (HR 1.055, 95% CI 1.0075 to 1.11, p=0.0227). Complications were hypotony (19.2%; N=20), choroidal detachments (10.6%; N=11), hyphaema (5.8%; N=6) and bleb leak (5.8%; N=6). Needling and 5-fluorouracil injections were performed in 12.5% (N=13) and 33.7% (N=35), respectively, and 11.5% (N=12) required revision surgery. CONCLUSION: The PreserFlo MicroShunt with MMC 0.4 mg/mL showed an overall success rate of 68.3% at 1 year, and led to significant IOP and medication reduction with a low rate of adverse effects.

Long-term outcomes in Primary congenital glaucoma, aniridia and anterior segment dysgenesis.

AIM: To determine the long-term outcomes of a cohort of complex patients with primary congenital glaucoma, aniridia and anterior segment dysgenesis. METHODS: Retrospective consecutive series between 1990-2021 in two UK tertiary centres: Guy's and St Thomas' NHS Foundation Trust and King's College Hospital NHS Foundation Trust. We recorded the number and types of surgical and laser treatments along with preoperative and postoperative data, including intraocular pressures (IOP) and anti-glaucoma medications. RESULTS: A total of 41 eyes of 21 patients were included. Primary diagnoses were primary congenital glaucoma in 16 eyes (39.0%), aniridia in 14 eyes (34.2%), and anterior segment dysgenesis in 8 eyes (19.5%). Sixteen eyes (39.0%) had one or more glaucoma surgery or laser procedures for advanced glaucoma, and the long-term follow-up was 12.8 ± 3.6 years. There was a significant decrease in postoperative IOP (mmHg) at 3 months (16.5 ± 1.6; p = 0.0067), 6 months (18.7 ± 2.1; p = 0.0386), 12 months (18.6 ± 1.7; p = 0.0229), 3 years (14.7 ± 1.2; p = 0.0126), 5 years (15.5 ± 1.8; p = 0.0330) and 10 years (15.4 ± 2.3; p = 0.7780), compared to preoperatively (24.1 ± 2.6). Surgical success (complete and qualified) was 62.5%, 50.0%, 43.8%, 46.2%, 45.5% and 28.6% at 3 months, 6 months, 12 months, 3 years, 5 years and 10 years, respectively. There was no significant change in the number of anti-glaucoma drugs postoperatively (p > 0.05). Four eyes (25.0%) had postoperative complications (hyphaema, hypotony) that resolved after conservative management. CONCLUSIONS: Surgical management of these complex eyes with advanced glaucoma is challenging. Overall, the cohort had good surgical outcomes with a significant decrease in IOP by 36.1% after long-term follow-up.

Neuroprotection in Glaucoma: NAD+/NADH Redox State as a Potential Biomarker and Therapeutic Target.

Glaucoma is the leading cause of irreversible blindness worldwide. Its prevalence and incidence increase exponentially with age and the level of intraocular pressure (IOP). IOP reduction is currently the only therapeutic modality shown to slow glaucoma progression. However, patients still lose vision despite best treatment, suggesting that other factors confer susceptibility. Several studies indicate that mitochondrial function may underlie both susceptibility and resistance to developing glaucoma. Mitochondria meet high energy demand, in the form of ATP, that is required for the maintenance of optimum retinal ganglion cell (RGC) function. Reduced nicotinamide adenine dinucleotide (NAD+) levels have been closely correlated to mitochondrial dysfunction and have been implicated in several neurodegenerative diseases including glaucoma. NAD+ is at the centre of various metabolic reactions culminating in ATP production-essential for RGC function. In this review we present various pathways that influence the NAD+(H) redox state, affecting mitochondrial function and making RGCs susceptible to degeneration. Such disruptions of the NAD+(H) redox state are generalised and not solely induced in RGCs because of high IOP. This places the NAD+(H) redox state as a potential systemic biomarker for glaucoma susceptibility and progression; a hypothesis which may be tested in clinical trials and then translated to clinical practice.

Surgical diseases of the womb according to Aetius of Amida (6th century A.D.).

BACKGROUND: In the interest of presenting historical background for modern-day medicine and surgery, the authors comment on the concepts of the eminent Byzantine physician Aetius of Amida (sixth century A.D.) in surgical treatment of diseases of the womb. STUDY DESIGN: The 16th book of Aetius' work Tetrabiblus, in the original Greek language, a treatise on gynecology and obstetrics of his era, was investigated. Comparison was then made of the relative knowledge among ancient and Byzantine physicians. DISCUSSION: Aetius analytically describes many surgical diseases of the womb (prolapse, abscesses, phimosis, atresia, hemorrhoids, stones, thymos, chaps) and gives a detailed symptomatology and conservative and surgical treatment. His work followed Hippocratic, Roman, and early Byzantine physicians, especially Soranus, the "Father of ancient gynecology and obstetrics" and influenced later physicians of his era and beyond. CONCLUSIONS: Aetius of Amida gives significant information about surgical approaches to diseases of the womb, the most detailed of any medical writer of his epoch. His descriptions, following the Hippocratic and mainly the Hellenistic and Roman traditions, influenced Islamic and European medicine, and through them the rest of the world, constituting the roots of the specialty of gynecology.

Perceived color of hallucinations in the Charles Bonnet Syndrome is related to residual color contrast sensitivity.

BACKGROUND: We sought to determine whether the change in cortical excitability secondary to deafferentation in patients with Charles Bonnet Syndrome (CBS) who hallucinate in a predominant color or combination of colors is related to an alteration in color contrast thresholds and whether the change is specific to the color of the hallucination. METHODS: We prospectively categorized each patient's hallucinations using the Institute of Psychiatry Visual Hallucinations Interview. We measured color contrast thresholds with a computerized test designed to assess red-green and blue-yellow color confusion axes against a background of luminance noise. We calculated the ratio of red-green threshold to blue-yellow threshold (R-G/B-Y ratio) for each patient. Because central vision was impaired in all patients, we used a sectoral annular stimulus that projected to the retina at 12.5 degrees eccentricity. RESULTS: There were 10 patients with age-related macular degeneration and CBS who were hallucinating in a predominant color or combination of colors at the time of recruitment. Patients hallucinating in red, green, or a combination of red and green had R-G/B-Y ratios of less than 1.0 (n = 5). Patients hallucinating in blue, yellow, or a combination of blue and yellow had R-G/B-Y ratios of greater than 1.0 (n = 2). Patients hallucinating in purple had ratios between the red-green and blue-yellow hallucinators (n = 2). The 1 patient hallucinating in white had the lowest thresholds for red-green and blue-yellow confusion axes. Comparing the R-G/B-Y ratios for the "red/green hallucinators" and "blue/yellow hallucinators" returned a significant result with Fisher's exact test (P = 0.047, n = 7). CONCLUSIONS: Deafferentation and secondary cortical hyperexcitability in CBS have a correlate in psychophysical threshold. This change in sensitivity relates specifically to the hallucinated color axis rather than across all colors. This is the first published evidence for cerebral hyperexcitability leading to a decrease in color contrast thresholds.