Biomarkers of systemic inflammation predict survival with first-line immune checkpoint inhibitors in non-small-cell lung cancer.

INTRODUCTION: Pembrolizumab is an established first-line option for patients with advanced non-small-cell lung cancer (NSCLC) expressing programmed death-ligand 1 ≥50%. Durable responses are seen in a subset of patients; however, many derive little clinical benefit. Biomarkers of the systemic inflammatory response predict survival in NSCLC. We evaluated their prognostic significance in patients receiving first-line pembrolizumab for advanced NSCLC. METHODS: Patients treated with first-line pembrolizumab for advanced NSCLC with programmed death-ligand 1 expression ≥50% at two regional Scottish cancer centres were identified. Pretreatment inflammatory biomarkers (white cell count, neutrophil count, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, albumin, prognostic nutritional index) were recorded. The relationship between these and progression-free survival (PFS) and overall survival (OS) were examined. RESULTS: Data were available for 219 patients. On multivariate analysis, albumin and neutrophil count were independently associated with PFS (P < 0.001, P = 0.002, respectively) and OS (both P < 0.001). A simple score combining these biomarkers was explored. The Scottish Inflammatory Prognostic Score (SIPS) assigned 1 point each for albumin <35 g/l and neutrophil count >7.5 × 109/l to give a three-tier categorical score. SIPS predicted PFS [hazard ratio 2.06, 95% confidence interval (CI) 1.68-2.52 (P < 0.001)] and OS [hazard ratio 2.33, 95% CI 1.86-2.92 (P < 0.001)]. It stratified PFS from 2.5 (SIPS2), to 8.7 (SIPS1) to 17.9 months (SIPS0) (P < 0.001) and OS from 5.1 (SIPS2), to 12.4 (SIPS1) to 28.7 months (SIPS0) (P < 0.001). The relative risk of death before 6 months was 2.96 (95% CI 1.98-4.42) in patients with SIPS2 compared with those with SIPS0-1 (P < 0.001). CONCLUSIONS: SIPS, a simple score combining albumin and neutrophil count, predicts survival in patients with NSCLC receiving first-line pembrolizumab. Unlike many proposed prognostic scores, SIPS uses only routinely collected pretreatment test results and provides a categorical score. It stratifies survival across clinically meaningful time periods that may assist clinicians and patients with treatment decisions. We advocate validation of the prognostic utility of SIPS in this and other immune checkpoint inhibitor treatment settings.

Leaf cell membrane stability-based mechanisms of zinc nutrition in mitigating salinity stress in rice.

Excess salt affects about 955 million ha of arable land worldwide, and 49% of agricultural land is Zn-deficient. Soil salinity and zinc deficiency can intensify plant abiotic stress. The mechanisms by which Zn can mitigate salinity effects on plant functions are not well understood. We conducted an experiment to determine how Zn and salinity effects on rice plant retention of Zn, K+ and the salt ion Na+ affect chlorophyll formation, leaf cell membrane stability and grain yield. We examined the mechanisms of Zn nutrition in mitigating salinity stress by examining plant physiology and nutrition. We used native Zn-deficient soils (control), four salinity (EC) and Zn treatments - Zn 10 mg·kg-1 (Zn10 ), EC 5 dS·m-1 (EC5 ), Zn10 +EC5 and Zn15 +EC5 , a coarse rice (KS-282) and a fine rice (Basmati-515) in the study. Our results showed that Zn alone (Zn10 ) significantly increased rice tolerance to salinity stress by promoting Zn/K+ retention, inhibiting plant Na+ uptake and enhancing leaf cell membrane stability and chlorophyll formation in both rice cultivars in native alkaline, Zn-deficient soils (P < 0.05). Further, under the salinity treatment (EC5 ), Zn inputs (10-15 mg·kg-1 ) could also significantly promote rice plant Zn/K+ retention and reduce plant Na+ uptake, and thus increased leaf cell membrane stability and grain yield. Coarse rice was more salinity-tolerant than fine rice, having significantly higher Zn/K+ nutrient retention. The mechanistic basis of Zn nutrition in mitigating salinity impacts was through promoting plant Zn/K+ uptake and inhibiting plant Na+ uptake, which could result in increased plant physiological vigour, leaf cell membrane stability and rice productivity.

The UK Neovascular AMD Database Report 3: inter-centre variation in visual acuity outcomes and establishing real-world measures of care.

PurposeInternational variations in visual acuity (VA) outcomes of eyes treated for neovascular age-related macular degeneration (nAMD) are well-documented, but intra-country inter-centre regional variations are not known. These data are important for national quality outcome indicators. We aimed to determine intra-country and inter-centre regional variations in outcomes for treatment of nAMD.Patients and methodsProspective multicentre national database study of 13 UK centres that treated patients according to a set protocol (three loading doses, followed by Pro-Re-Nata retreatment). A total of 5811 treatment naive eyes of 5205 patients received a total of 36 206 ranibizumab injections over 12 months.ResultsMean starting VA between centres varied from 48.9 to 59.9 ETDRS letters. Mean inter-centre VA change from baseline to 12 months varied from +6.9 letters to -0.6 letters (mean of +2.5 letters). The proportion of eyes achieving VA of 70 letters or more varied between 21.9 and 48.7% at 12 months. Median number of injections (visits) at each centre varied from 5 to 8 (9 to 12), with an overall median of 6 (11). Age, starting VA, number of injections, and visits, but not gender were significantly associated with variation in these VA outcomes (P<0.01). Significant variation between centres persisted even after adjusting for these factors.ConclusionThere are modest differences in VA outcomes between centres in the UK. These differences are influenced, but not completely explained, by factors such as patient age, starting VA, number of injections, and visits. These data provide an indication of the VA outcomes that are achievable in real-world settings.

Structural changes of the choroid in sarcoid- and tuberculosis-related granulomatous uveitis.

AIM: The aim of this study is to characterise the choroidal features of patients diagnosed with sarcoid- and tuberculosis (TB)-associated granulomatous uveitis using spectral domain optical coherence tomography (OCT). METHODS: Twenty-seven patients (27 eyes) diagnosed with sarcoid- (13 eyes) and TB (14 eyes)-related uveitis were included in this retrospective, cross-sectional study. Over a six-month period, patients diagnosed with sarcoid and TB granulomatous uveitis were scanned using enhanced depth imaging OCT. Clinical and demographical characteristics were recorded, including the method of diagnosis, disease activity, site of inflammation (anterior or posterior), treatments, and visual acuity (VA). Manual segmentation of the choroidal layers was performed using custom image analysis software. RESULTS: The main outcome measure was OCT-derived thickness measurements of the choroid and choroidal sublayers (Haller's large vessel and Sattler's medium vessel layers) at the macula region. The ratio of Haller's large vessel to Sattler's medium vessel layer was significantly different at the total macula circle in eyes diagnosed with TB uveitis (1.47 (=140.71/95.72 µm)) compared with sarcoid uveitis (1.07 (=137.70/128.69 µm)) (P=0.001). A thinner choroid was observed in eyes with a VA ≥0.3 LogMAR (Snellen 6/12; 198.1 µm (interquartile range (IQR)=147.0-253.4 µm) compared with those with VA <0.3 LogMAR (292.4 µm (IQR=240.1-347.6 µm)) at the total macula circle (P=0.004). At the foveal central subfield, the median choroidal thickness was 336.8 µm (IQR=272.3-375.4 µm) in active compared with 239.3 µm (IQR=195.3-330.9 µm) in quiescent disease (P=0.04). CONCLUSION: A disproportionately enlarged Sattler's layer may indicate a diagnosis of sarcoid-related uveitis, and choroidal thickening may be a feature of active granulomatous uveitis.

Defining response to anti-VEGF therapies in neovascular AMD.

The introduction of anti-vascular endothelial growth factor (anti-VEGF) has made significant impact on the reduction of the visual loss due to neovascular age-related macular degeneration (n-AMD). There are significant inter-individual differences in response to an anti-VEGF agent, made more complex by the availability of multiple anti-VEGF agents with different molecular configurations. The response to anti-VEGF therapy have been found to be dependent on a variety of factors including patient's age, lesion characteristics, lesion duration, baseline visual acuity (VA) and the presence of particular genotype risk alleles. Furthermore, a proportion of eyes with n-AMD show a decline in acuity or morphology, despite therapy or require very frequent re-treatment. There is currently no consensus as to how to classify optimal response, or lack of it, with these therapies. There is, in particular, confusion over terms such as 'responder status' after treatment for n-AMD, 'tachyphylaxis' and 'recalcitrant' n-AMD. This document aims to provide a consensus on definition/categorisation of the response of n-AMD to anti-VEGF therapies and on the time points at which response to treatment should be determined. Primary response is best determined at 1 month following the last initiation dose, while maintained treatment (secondary) response is determined any time after the 4th visit. In a particular eye, secondary responses do not mirror and cannot be predicted from that in the primary phase. Morphological and functional responses to anti-VEGF treatments, do not necessarily correlate, and may be dissociated in an individual eye. Furthermore, there is a ceiling effect that can negate the currently used functional metrics such as >5 letters improvement when the baseline VA is good (ETDRS>70 letters). It is therefore important to use a combination of both the parameters in determining the response.The following are proposed definitions: optimal (good) response is defined as when there is resolution of fluid (intraretinal fluid; IRF, subretinal fluid; SRF and retinal thickening), and/or improvement of >5 letters, subject to the ceiling effect of good starting VA. Poor response is defined as <25% reduction from the baseline in the central retinal thickness (CRT), with persistent or new IRF, SRF or minimal or change in VA (that is, change in VA of 0+4 letters). Non-response is defined as an increase in fluid (IRF, SRF and CRT), or increasing haemorrhage compared with the baseline and/or loss of >5 letters compared with the baseline or best corrected vision subsequently. Poor or non-response to anti-VEGF may be due to clinical factors including suboptimal dosing than that required by a particular patient, increased dosing intervals, treatment initiation when disease is already at an advanced or chronic stage), cellular mechanisms, lesion type, genetic variation and potential tachyphylaxis); non-clinical factors including poor access to clinics or delayed appointments may also result in poor treatment outcomes. In eyes classified as good responders, treatment should be continued with the same agent when disease activity is present or reactivation occurs following temporary dose holding. In eyes that show partial response, treatment may be continued, although re-evaluation with further imaging may be required to exclude confounding factors. Where there is persistent, unchanging accumulated fluid following three consecutive injections at monthly intervals, treatment may be withheld temporarily, but recommenced with the same or alternative anti-VEGF if the fluid subsequently increases (lesion considered active). Poor or non-response to anti-VEGF treatments requires re-evaluation of diagnosis and if necessary switch to alternative therapies including other anti-VEGF agents and/or with photodynamic therapy (PDT). Idiopathic polypoidal choroidopathy may require treatment with PDT monotherapy or combination with anti-VEGF. A committee comprised of retinal specialists with experience of managing patients with n-AMD similar to that which developed the Royal College of Ophthalmologists Guidelines to Ranibizumab was assembled. Individual aspects of the guidelines were proposed by the committee lead (WMA) based on relevant reference to published evidence base following a search of Medline and circulated to all committee members for discussion before approval or modification. Each draft was modified according to feedback from committee members until unanimous approval was obtained in the final draft. A system for categorising the range of responsiveness of n-AMD lesions to anti-VEGF therapy is proposed. The proposal is based primarily on morphological criteria but functional criteria have been included. Recommendations have been made on when to consider discontinuation of therapy either because of success or futility. These guidelines should help clinical decision-making and may prevent over and/or undertreatment with anti-VEGF therapy.

Infundibular Recess Angle Reduction After Endoscopic Third Ventriculostomy: Does It Reflect Clinical Success?

BACKGROUND: Although the ventricular size is significantly reduced after endoscopic third ventriculostomy (ETV) in most successfully treated patients, ventricular size reduction is not always seen after a successful ETV. Practical and reliable radiologic parameters are still needed to assess the clinical success of an ETV. METHODS: We retrieved the clinical and radiologic data of patients who underwent an ETV. Patients with the following criteria were included: (1) preoperative magnetic resonance imaging studies available, (2) postoperative magnetic resonance imaging studies done within the first 2 postoperative weeks, and (3) the infundibular recess clearly visible on preoperative and postoperative sagittal magnetic resonance imaging. Preoperative and postoperative measurements of the angle of the infundibular recess of the third ventricle were performed on midsagittal T1-weighted, T2-weighted, fast imaging employing steady-state acquisition, or constructive interference in steady state images. RESULTS: The extent of reduction of the infundibular recess angle predicted the clinical outcome of ETV during the early postoperative period with a high degree of accuracy. The average reduction was about 48% in successful procedures versus only 15% in failed procedures. CONCLUSIONS: The degree of reduction of the angle of the infundibular recess of the third ventricle correlated with the amount of third ventricular decompression after ETV. Most importantly, such a reduction was noted to occur during the early postoperative period when radiologic changes are less pronounced. Assessment of change in infundibular recess angle measurement is easy to perform and may prove helpful in cases with no clear-cut clinical evidence of success of ETV.

Endoscopic management of a choroid plexus cyst of the third ventricle: case report and documentation of dynamic behavior.

PURPOSE: The aim of this study is to document the dynamic behavior of a choroid plexus cyst of the third ventricle. Although these lesions may float freely within the ventricle leading to intermittent obstruction of the cerebrospinal fluid (CSF) circulation at variable points in a single patient, such a phenomenon has only been documented using cranial ultrasonography and was never observed intraoperatively. METHODS: We endoscopically treated a case of third ventricular choroid plexus cyst in a 9-year-old boy who presented with headaches and disturbed conscious level. He underwent a transventricular approach through a single burr hole. RESULTS: During the procedure, the cyst was noted to intermittently herniate into the lateral ventricle and recede back through the foramen of Monro. Endoscopic ablation of the cyst was achieved and followed by endoscopic third ventriculostomy (ETV). The patient made an excellent recovery after the procedure. CONCLUSIONS: We were able to endoscopically observe the dynamic behavior displayed by a choroid plexus cyst of the third ventricle. To the best of our knowledge, intraoperative documentation of the obstruction of the CSF pathway by a single choroid plexus cyst that intermittently herniates through the foramen of Monro and back into the third ventricular cavity has not been previously demonstrated neither microsurgically nor endoscopically.

Prevalence and incidence of blindness and other degrees of sight impairment in patients treated for neovascular age-related macular degeneration in a well-defined region of the United Kingdom.

AIMS: This study aimed to evaluate the incidence and prevalence of blindness, sight impairment, and other visual acuity (VA) states in patients receiving ranibizumab for neovascular age-related macular degeneration (nAMD) in Gloucestershire. METHODS: Serial VA and injection data for all treatment-naive patients receiving their first intravitreal injections of ranibizumab for nAMD in the Gloucestershire National Health Service Ophthalmology department between 2008 and 2010 were extracted from an electronic medical record system. RESULTS: The prevalence of blindness (VA in the better-seeing eye ≤25 Early Treatment Diabetic Retinopathy Study (ETDRS) letters) at the time of first intravitreal injection was 0.8%, increasing to 3.5% after 3 years. The prevalence of sight impairment (VA in the better-seeing eye 26-39 ETDRS letters) increased from 4.1% at baseline to 5.5% after 3 years. The incidence of initiating ranibizumab treatment for nAMD in people aged ≥50 years in Gloucestershire was 111 people per 100 000 population in 2009, and 97 people in 2010. The incidence of patients meeting the visual criteria for blindness and sight impairment registration from treated nAMD in people aged ≥50 years in Gloucestershire was 3.5 and 9.7 people, respectively per 100 000 population in 2010. CONCLUSION: This is the first real-world study on the incidence and prevalence of eligibility for blindness and sight impairment registration in treated nAMD in the UK based on VA data. The incidence and prevalence of eligibility for certification of blindness or sight impairment in patients treated with ranibizumab for nAMD is low in Gloucestershire, with only 3.6% of the incident population progressing to blindness in 2010.

XRCC3 Thr241Met gene polymorphism and risk of colorectal cancer in Kashmir: a case control study.

XRCC (X-ray cross-complementing group) genes contribute to important DNA repair mechanisms that play roles in the repair of single strand breaks (SSBs) induced by a variety of external and internal factors, including ionizing radiation, alkylating agents and reactive oxygen species. These repair genes have a pivotal role in maintaining genomic stability through different pathways of base excision repair (BER). The aim of this study was to investigate the XRCC3 Thr241Met gene polymorphism in colorectal cancer (CRC) in Kashmir. We investigated the genotype distribution of XRCC3 gene in 120 CRC cases in comparison with 150 healthy subjects and found a significant association between XRCC3 genotypes and CRC (p≤0.05). Both heterozygous genotype (Thr/Met) as well as homozygous variant genotype (Met/Met) were moderately associated with elevated risk of CRC [OR=2.53; OR=2.29 respectively]. Also, Thr/Met and Met/Met genotypes demonstrated a significant association with the risk of CRC (p=0.003). This study displayed a significantly elevated risk for CRC in individuals with XRCC3 Thr/Met and Met/Met Genotype of about 2.5 times that with the Thr/Thr wild genotype.

Diagnostic features of the autoimmune retinopathies.

The term autoimmune retinopathy encompasses a spectrum of rare autoimmune diseases that affect retinal function, often but not exclusively at the level of the photoreceptor. They typically present with painless visual loss, which may be accompanied by normal fundus examination. Some are progressive, often rapidly. They present a diagnostic challenge because there are no standardised clinical or laboratory based diagnostic criteria. Included within the spectrum are cancer-associated retinopathy, melanoma-associated retinopathy and presumed non-paraneoplastic autoimmune retinopathy. Differentiation from other retinopathies can be challenging, with overlap in symptoms, signs, and investigation findings, and an absence of pathognomonic features. However, technological developments in ophthalmic imaging and serological investigation over the past decade are adding novel dimensions to the investigation and classification of patients with these rare diseases. This review addresses the clinical, imaging, and serological features of the autoimmune retinopathies, and discusses the relative strengths and limitations of candidate diagnostic features.

Ranibizumab for the treatment of choroidal neovascularisation secondary to pathological myopia: interim analysis of the REPAIR study.

AIMS: To evaluate the efficacy and safety of intravitreal ranibizumab in patients with choroidal neovascularisation secondary to pathological myopia (myopic CNV). Data are from a pre-planned, 6-month interim analysis. METHODS: Phase II, open-label, single arm, multicentre, 12-month study, recruiting patients (aged ≥18 years) with active primary or recurrent subfoveal or juxtafoveal myopic CNV, with a best-corrected visual acuity (BCVA) score of 24-78 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in the study eye and a diagnosis of high myopia of at least -6 dioptres. Patients received 0.5 mg ranibizumab administered intravitreally to the study eye, followed by monthly injections given as needed (based on a predefined algorithm) for up to 11 months. RESULTS: At 6 months, mean BCVA improved from baseline by 12.2 letters, as did central macular thickness (in this interim analysis defined as a measure of either central subfield macular thickness or centre point macular thickness) from baseline by 108 µm in the 48 study eyes of 48 patients. Fewer patients had centre-involving intraretinal oedema (13.0% vs 91.5%), intraretinal cysts (10.9% vs 57.4%), or subretinal fluid (13.0% vs 66.0%) at 6 months than at baseline. Patients received a mean of 1.9 retreatments, were satisfied with ranibizumab treatment, and well being was maintained. No new safety signals were identified. CONCLUSIONS: Results from the planned interim analysis support the role of ranibizumab in the treatment of myopic CNV, with excellent efficacy achieved with a low number of injections and few serious adverse events.

Autoimmune retinopathy.

Autoimmune retinopathy encompasses a spectrum of rare autoimmune diseases that primarily affect retinal photoreceptor function, and include cancer-associated retinopathy (CAR), melanoma-associated retinopathy (MAR) and presumed non-paraneoplastic autoimmune retinopathy (npAIR). Autoimmune retinopathy typically presents in the fifth and sixth decades with rapidly progressive, bilateral, painless visual deterioration but an unremarkable fundus examination. CAR, MAR and npAIR have an overlapping clinical phenotype, and extensive investigation is required to exclude other causes of retinopathy, and to identify any occult malignancy, before a presumptive diagnosis can be made. Delayed diagnosis, and treatment initiation relatively late in the disease course, may contribute to the poor visual prognosis. Various treatments have been attempted, including systemic immunosuppression with steroid and steroid-sparing agents, intravenous immunoglobulin, and plasmapheresis, but these lack an evidence base. A variety of antiretinal antibodies have been identified in patients with autoimmune retinopathy, including antibodies to recoverin, α-enolase and transducin-α, but seronegative disease is also common. Clinical access to specialised serological investigation is very limited internationally, and this exacerbates the management challenge presented by patients with suspected autoimmune retinopathy. Several decades of experimental research have resulted in very considerable advances in our understanding of the pathophysiological mechanisms that may underlie autoimmune retinopathy. However, the precise triggers which result in loss of ocular immune privilege and sudden autoimmune attack on retinal cells have yet to be elucidated. This review summarizes the classification, investigation and management of autoimmune retinopathy, and considers the evolving concepts about its immunological aetiology.

Role of intraoperative sentinel lymph node mapping in the management of carcinoma of the esophagus.

BACKGROUND/AIM: Precise evaluation of lymph node status is one of the most important factors in determining clinical outcome in treating gastro-intestinal (GI) cancer. Sentinel lymph node (SLN) mapping clearly has become highly feasible and accurate in staging GI cancer. This study aims to investigate the feasibility and accuracy of detection of SLN using methylene blue dye in patients with carcinoma of the esophagus and assess its potential role in determining the rational extent of lymphadenectomy in esophageal cancer surgery. MATERIALS AND METHODS: Thirty-two patients of esophageal cancer diagnosed on endoscopic biopsy were enrolled in this prospective study. After laparotomy, patent methylene blue was injected into the subserosal layer adjacent to the tumor. SLNs were defined as blue stained nodes within a period of 5 min. Standard radical esophagogastrectomy with lymphadenectomy was performed in all the patients. All the resected nodes were examined postoperatively by routine hematoxylin and eosin stain for elucidating the presence of metastasis, and the negative SLNs were examined further with cytokeratin immunohistochemical staining. RESULTS: SLNs were detected in 26 (81.25%) patients out of 32 patients who were studied. The number of SLNs ranged from 1 to 4 with a mean value of 1.7 per case. The SLNs of esophageal cancer were only found in N1 area in 21 (80.77%) cases, and in N2 or N3 area in only 19.33%. The overall accuracy of the procedure was 75% in predicting nodal metastasis. SLN had a sensitivity of 85.71% in mid esophageal tumors and 93.33% in lower esophageal tumors. The SLN biopsy had sensitivity of 87.5% in the case of squamous cell carcinoma and 92.86% in the cases of adenocarcinoma of the esophagus. The accuracy of the procedure for squamous cell carcinoma and adenocarcinoma was 60% and 76.47%, respectively. CONCLUSION: SLN mapping is an accurate diagnostic procedure for detecting lymph node metastasis in patients with esophageal cancer and may indicate rational extent of lymphadenectomy in these patients. SLN mapping provides "right nodes" to the pathologists for detailed analysis and appropriate staging, thereby helping in individualizing the multi-modal treatment for esophageal cancer.

Recurrence pattern in squamous cell carcinoma of skin of lower extremities and abdominal wall (Kangri cancer) in Kashmir valley of Indian subcontinent: impact of various treatment modalities.

BACKGROUND: The spectrum of skin cancer in Kashmir valley is drastically different from the rest of the country. Maxwell was the first to report skin cancer of lower extremities in Kashmiri population, developing on/over erythema ab igne, and attributed it to the use/or exposure of Kangri. These tumors have an aggressive biological behavior with a substantial risk of loco-regional metastasis in 30-50% cases. Because of unique geographical distribution of Kangri cancer, there is dearth of literature regarding the natural history, loco-regional and distant metastatic pattern and treatment recommendations in these tumors. AIMS: To study the metastatic pattern of these skin tumors and to assess the impact of various treatment modalities and use of prophylactic nodal treatment in this clinical entity. METHODS: The retrospective study (study period 1993-2005) included 266 patients of squamous cell carcinoma of skin of lower extremities and abdominal wall. Two hundred and forty-four cases with a follow-up of 2-7 years were included for final analysis with stress on loco-regional relapse pattern and methods of treatment evolved and used at our institute from time to time. Statistical analysis was done using yates corrected Chi-square test and odds ratio analysis. RESULTS: Our results favor the use of post operative radiotherapy to primary and prophylactic treatment of regional nodes on the lines of head and neck tumors in these cases. CONCLUSION: Post operative radiotherapy significantly decreases the loco-regional recurrences and a trial of prophylactic nodal irradiation is justified in a selected group of such patients.

Age-related macular degeneration: diagnosis and management.

BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of blind registration in Western Europe and the third leading cause of blindness worldwide. METHODS: The management of AMD is discussed with a review of current and new treatments. RESULTS: Although there is no treatment for advanced dry AMD (geographic atrophy), there have been considerable advances in the management of neovascular AMD (nAMD). Established therapies for nAMD include laser photocoagulation and photodynamic therapy (PDT), but these have largely been superseded by agents which block the action of vascular endothelial growth factor (anti-VEGF agents). Current preventative strategies involve cessation of smoking and use of specific nutritional supplements to reduce the risk of developing nAMD. CONCLUSIONS: There have been exciting advances in the treatment of nAMD and increased understanding of the genetics and pathogenic mechanisms involved will hopefully lead to the development of new therapies in the future.

Punctate inner choroidopathy-associated choroidal neovascular membranes during pregnancy.

UNLABELLED: PURPOSE AND MATERIALS: Punctate inner choroidopathy (PIC), first described by Watzke et al(1), is a disease in young women of child-bearing age. We present three cases of PIC-associated choroidal neovascular membrane (CNVM) occurring during pregnancy, and discuss associated investigative and treatment dilemmas. RESULTS: All three patients described showed evidence of recurrence of CNVM during their pregnancy. None underwent FFA but benefited from OCT monitoring. Different therapeutic strategies were adopted in each of our cases. Case 1, with a history of spontaneous CNVM regression, was managed conservatively. Cases 2 and 3 chose steroid treatment to their better-seeing eye. All cases remained stable postpartum. DISCUSSION: Management of PIC-related CNVM creates diagnostic and therapeutic challenges. The problem is exacerbated as the pathology is often sequentially bilateral and sight threatening. Owing to the rarity of such cases, there is a paucity of evidence on which to base the treatment strategies. A history of pregnancy should always be elicited before investigation with FFA, and women warned of the potential for disease exacerbation with limited therapeutic options during pregnancy. CONCLUSIONS: spontaneous resolution of CNVM is common in PIC, and should be borne in mind while treating pregnant women. Peri/intraocular steroid injection represents a reasonable option for sight-threatening CNVM in the better-seeing eye.

A comparison of Ktrans measurements obtained with conventional and first pass pharmacokinetic models in human gliomas.

PURPOSE: To compare in a group of patients with cerebral gliomas the estimates of Ktrans between a conventionally established pharmacokinetic model and a recently developed first pass method. MATERIALS AND METHODS: Glioma patients (23) were studied using T1-weighted dynamic contrast-enhanced magnetic resonance imaging (MRI), and two alternative pharmacokinetic models were used for analysis to derive the volume transfer constant Ktrans. These were a modified version of the established model (yielding KTK) and a recently published method based on first pass leakage profile (FP) of contrast bolus (yielding Kfp). RESULTS: We found a strong correlation between intra-tumoral median KTK and Kfp (rho = 0.650, P < 0.01), but the values from the conventional model were consistently and significantly higher (mean of inter-tumoral Kfp and KTK medians were 0.018 minute(-1) and 0.284 minute(-1), respectively, P < 0.001). The spatial distribution of KTK and Kfp showed poor correlation in the presence of large vascular structures and good correlation elsewhere. CONCLUSION: KTK and Kfp produce similar biologic information within voxels not dominated by vascular tissue. The FP method avoids erroneous overestimation of Ktrans in areas of significant intravascular contrast. Findings are in keeping with the predictions of previous mathematical simulations.