OCRIPLASMIN FOR VITREOMACULAR TRACTION IN CLINICAL PRACTICE: The INJECT Study.

PURPOSE: Randomized clinical trials have demonstrated the safety and efficacy of ocriplasmin in patients with vitreomacular traction (VMT), including those with macular hole (MH). The INJECT study prospectively evaluated ocriplasmin in the setting of clinical practice. METHODS: INJECT was a Phase 4, multicenter, prospective observational study. Patients were followed up for 12 months. Assessments included nonsurgical VMT resolution, nonsurgical MH closure, best-corrected visual acuity, occurrence of vitrectomy, and adverse events. RESULTS: The efficacy population (N = 395) received an ocriplasmin injection and had optical coherence tomography-confirmed VMT at baseline. At Day 28, the rate of nonsurgical VMT resolution was 40.7% in the overall group, and the rate of nonsurgical MH closure was 36.0% in the VMT with MH group. At Month 12, the rate of ≥2-line best-corrected visual acuity gain (irrespective of vitrectomy) was 36.8% in the overall group and 59.6% in the VMT with MH group. The percentage of patients who underwent vitrectomy in the study eye was 29.1% in the overall group and 55.6% in the VMT with MH group. Photopsia (9.8%) and vitreous floaters (6.8%) were the most frequent adverse events. CONCLUSION: The INJECT study showed that ocriplasmin is effective in a clinical setting in patients with VMT, with or without MH. No new safety signals were identified from this large and surgeon-selected patient group, although the significant limitations of the study design without an image reading center and scheduled study visit timings should be noted.

Long-term safety and efficacy of factor IX gene therapy in hemophilia B.

BACKGROUND: In patients with severe hemophilia B, gene therapy that is mediated by a novel self-complementary adeno-associated virus serotype 8 (AAV8) vector has been shown to raise factor IX levels for periods of up to 16 months. We wanted to determine the durability of transgene expression, the vector dose-response relationship, and the level of persistent or late toxicity. METHODS: We evaluated the stability of transgene expression and long-term safety in 10 patients with severe hemophilia B: 6 patients who had been enrolled in an initial phase 1 dose-escalation trial, with 2 patients each receiving a low, intermediate, or high dose, and 4 additional patients who received the high dose (2×10(12) vector genomes per kilogram of body weight). The patients subsequently underwent extensive clinical and laboratory monitoring. RESULTS: A single intravenous infusion of vector in all 10 patients with severe hemophilia B resulted in a dose-dependent increase in circulating factor IX to a level that was 1 to 6% of the normal value over a median period of 3.2 years, with observation ongoing. In the high-dose group, a consistent increase in the factor IX level to a mean (±SD) of 5.1±1.7% was observed in all 6 patients, which resulted in a reduction of more than 90% in both bleeding episodes and the use of prophylactic factor IX concentrate. A transient increase in the mean alanine aminotransferase level to 86 IU per liter (range, 36 to 202) occurred between week 7 and week 10 in 4 of the 6 patients in the high-dose group but resolved over a median of 5 days (range, 2 to 35) after prednisolone treatment. CONCLUSIONS: In 10 patients with severe hemophilia B, the infusion of a single dose of AAV8 vector resulted in long-term therapeutic factor IX expression associated with clinical improvement. With a follow-up period of up to 3 years, no late toxic effects from the therapy were reported. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov number, NCT00979238.).

First-Year Visual Acuity Outcomes of Providing Aflibercept According to the VIEW Study Protocol for Age-Related Macular Degeneration.

PURPOSE: Aflibercept has the potential advantage of reducing capacity problems by allowing 2 monthly visits for patients with neovascular macular degeneration (nAMD) compared with monthly pro re nata regimens that are the most commonly used in the United Kingdom. This study aimed to report the visual outcomes achieved in routine clinical practice using the VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD (VIEW) protocol at 1 year and compare with trials data and other real-world reports. DESIGN: Retrospective data analysis from an electronic medical record. PARTICIPANTS: Consecutive series of treatment-naïve patients initiated on aflibercept for nAMD at least 1 year before data extraction. METHODS: Data were anonymized and remotely extracted from 16 centers in the United Kingdom that use the same electronic medical record (EMR) system (Medisoft Ophthalmology; Medisoft Limited, Leeds, UK). MAIN OUTCOME MEASURES: The minimum data set defined before first data entry and mandated by the EMR included age, gender, visual acuity, injection episodes, and complications. RESULTS: The mean age was 80.0 years (median, 81.0 years) and 63.7% were women. During the first year of treatment with aflibercept, 1840 treatment-naïve eyes of 1682 patients received a median of 8 (mean, 7.0) injections at a median of 8 (mean, 7.3) visits. The mean baseline visual acuity was 53.7 letters, improving to 58.8 letters (+5.1-letter gain) at 1 year. In first-treated eyes, the respective figures were 52.7 letters at baseline and 58.2 letters at 1 year, a gain of +5.5 letters. The proportion achieving 70 letters or more increased from 16.4% at baseline to 33.7% at 1 year, and 92% avoided moderate visual loss at 1 year. CONCLUSIONS: The visual acuity outcomes are comparable to randomized trials and better than many previous real-world data collections, with a mean +5.1-letter gain at 1 year compared with +8.4 letters in the integrated analysis of the VIEW 1 and VIEW 2 studies. Early visual gains were maintained through the year. Collection of outcomes beyond clinical trials can have limitations but better reflect the full pool of patients actually treated and are important to determine whether a particular treatment is performing as expected. Such data also have the potential to improve services by setting up a mechanism to compare sites.

Correction: FGF Signalling Regulates Chromatin Organisation during Neural Differentiation via Mechanisms that Can Be Uncoupled from Transcription.

[This corrects the article DOI: 10.1371/journal.pgen.1003614.].

FGF signalling regulates chromatin organisation during neural differentiation via mechanisms that can be uncoupled from transcription.

Changes in higher order chromatin organisation have been linked to transcriptional regulation; however, little is known about how such organisation alters during embryonic development or how it is regulated by extrinsic signals. Here we analyse changes in chromatin organisation as neural differentiation progresses, exploiting the clear spatial separation of the temporal events of differentiation along the elongating body axis of the mouse embryo. Combining fluorescence in situ hybridisation with super-resolution structured illumination microscopy, we show that chromatin around key differentiation gene loci Pax6 and Irx3 undergoes both decompaction and displacement towards the nuclear centre coincident with transcriptional onset. Conversely, down-regulation of Fgf8 as neural differentiation commences correlates with a more peripheral nuclear position of this locus. During normal neural differentiation, fibroblast growth factor (FGF) signalling is repressed by retinoic acid, and this vitamin A derivative is further required for transcription of neural genes. We show here that exposure to retinoic acid or inhibition of FGF signalling promotes precocious decompaction and central nuclear positioning of differentiation gene loci. Using the Raldh2 mutant as a model for retinoid deficiency, we further find that such changes in higher order chromatin organisation are dependent on retinoid signalling. In this retinoid deficient condition, FGF signalling persists ectopically in the elongating body, and importantly, we find that inhibiting FGF receptor (FGFR) signalling in Raldh2-/- embryos does not rescue differentiation gene transcription, but does elicit both chromatin decompaction and nuclear position change. These findings demonstrate that regulation of higher order chromatin organisation during differentiation in the embryo can be uncoupled from the machinery that promotes transcription and, for the first time, identify FGF as an extrinsic signal that can direct chromatin compaction and nuclear organisation of gene loci.

Extracorporeal shock wave lithotripsy: Prematurely falling out of favour? A 7 year retrospective study from an Australian high-volume centre.

Objectives: The aim of this study is to audit 7 years of data with a 3 year follow up from a high-volume stone centre performing extracorporeal shock wave lithotripsy (ESWL) to evaluate efficacy in stone clearance compared to existing knowledge and understand reasons for this performance. Methods: Patients who received ESWL treatment for renal or proximal ureteric stones at a single centre between January 2012 and January 2019 (to allow minimum 3 year follow up) were retrieved. A retrospective analysis was performed cross referencing for stone size, location, treatment and need for further procedures. Ethical approval was granted through Metro North HHS HREC, Queensland, Australia. Results: A total of 1930 patients met inclusion criteria. Fifty-seven percent (n = 1100) underwent left-sided ESWL, compared to 43% (n = 830) on the right. Stone size and location were both statistically significant to treatment outcome. Small stones (<1 cm) had an overall clearance rate of 81.9%, medium stones (1-2 cm) had a clearance rate of 60.6% and stones (>2 cm) had a clearance rate of 31.3%. Small stones in an upper calyx had the highest clearance rate (87.5%, n = 120). Allowing for two procedures, 89% of stones were treated successfully. Conclusion: ESWL remains a legitimate option for the treatment of small and medium sized renal calculi. ESWL stone clearance rates at our centre are higher than published elsewhere and serve as proof to its efficacy. X-ray imaging on the day of the procedure, heavy consultant input and frequent intra-operative imaging are cited as key reasons for success. Further research is warranted to elucidate factors affecting stone clearance rate and to enable more standardised outcomes. Further investment may be required into ESWL provisions in most Australian states and especially in Queensland to enable its continued use in contrast to developing endourological techniques.

Atypical Presentation of a Type A Aortic Dissection in a Patient With an Undiagnosed Genetic Predisposition.

A 60-year-old female with a past medical history of hypertension presents to the ED with one day of throbbing left knee pain with associated numbness that worsened with ambulation. EKG shows lateral T-wave inversions with no prior for comparison. The patient had bloodwork drawn and a chest x-ray ordered. Her pain was improving with acetaminophen, and during further workup, she went into cardiac arrest. The advanced cardiac life support protocol was initiated, the patient was intubated, and point-of-care ultrasound revealed pericardial effusion. Despite all her efforts, she couldn't regain consciousness and was pronounced dead. An autopsy confirmed that the patient suffered a type A aortic dissection (AD), with findings indicating a predisposing genetic component. This case confirms that type A AD can present with different clinical symptoms and that a high index of suspicion is crucial in providing lifesaving measures.

SLAP Trial: Shock Wave Lithotripsy and Mechanical Percussion Therapy Post ESWL for Renal Calculi.

Methods: We conducted a prospective randomised control trial. Included patients were males and females greater than 18 years of age with single or multiple ipsilateral renal calculi of total ≤10 mm on plain X-ray and noncontrast CT KUB. ESWL was performed at a single centre, at supine position under general anaesthesia with maximum 3000 shocks at a rate of 100 shocks per minute. Patients were discharged and randomised to either the control arm or MPI therapy. MPI therapy was self-directed in a home setting for 10 minutes a day, three times per week. Both arms had standard follow-up at 12 weeks with a plain X-ray KUB. Patients in the control group were offered cross over to the MPI arm after 12 weeks if residual stone fragments were detected. Statistical analysis was performed using SPSS software via Chi squared and Fisher's exact tests. Ethical approval was obtained via the Prince Charles Hospital HREC Committee, HREC/2022/QPCH/84961. Results: 70 patients met inclusion criteria and underwent ESWL, and 5 were withdrawn. 33 patients were randomised to the MPI group and 32 to the control group. MPI significantly increased the stone clearance rate anywhere in the kidney (87.9% in the MPI group versus 59.4% in the control group, p=0.089), as well as the clearance rate in the lower pole (91.7% in the MPI group versus 63.2% in the control group, p=0.022). Delayed percussion did not improve the clearance rate over primary percussion (p=0.835). Conclusion: This study has shown that MPI can be effectively performed in a home setting without the need for medical supervision and results in improved stone clearance rates post ESWL. The main limitations to the study were the use of X-ray over CT during the follow-up and variability in MPI compliance and administration. Further research is warranted into standardising home MPI protocols. This trial is registered with ANZCTR387061.

Crisis in the Chest: Acute Chest Syndrome as a Sequela of Tricuspid Valve Endocarditis.

The management of acute chest syndrome (ACS) in sickle cell disease occurring concurrently with pulmonary embolism resulting from tricuspid valve endocarditis poses an atypical challenge. We present a case in which this complex interaction occurs and the prompt interventions that were utilized to give the best possible outcome.

Uro-symphyseal Fistula: A Systematic Review to Inform a Contemporary, Evidence-based Management Framework.

OBJECTIVE: To collate available data via systematic review considering etiology, presentation, and treatment of Uro-Symphyseal Fistula (USF) in order to inform a contemporary management framework. MATERIALS AND METHODS: A systematic review was performed according to the Cochrane Handbook and registered in PROSPERO (CRD42021232954). MEDLINE and CENTRAL databases were searched for manuscripts considering USF published between 2000 and 2022. Full text manuscripts were reviewed for clinical data. Univariate statistical analysis was performed where possible. RESULTS: A total of 31 manuscripts, comprising 248 USF cases, met inclusion criteria. Suprapubic pain and difficulty ambulating were common symptoms. MRI confirmed the diagnosis in 95% of cases. Radiotherapy for prostate cancer was the most common predisposing factor (93%). Among these patients, prior endoscopic bladder outlet surgery was common (83%; bladder neck incision/urethral dilatation n = 59, TURP/GLL PVP n = 34). In those with prior prostatic radiation, conservative management failed in 96% of cases. Cystectomy with urinary diversion (86% n = 184) was favored over bladder-sparing techniques (14% (n = 30) after prior radiation. In radiation naïve patients, conservative management failed in 72% of patients, resulting in either open fistula repair with flap (62%) or radical prostatectomy (28%). CONCLUSION: Prior radiotherapy is a significant risk factor for USF and almost always requires definitive major surgery (debridement, cystectomy, and urinary diversion). On the basis of the findings within this systematic review, we present management principles that may assist clinicians with these complex cases. Further research into pathogenesis, prevention, and optimal treatment approach is required.

Identification of anti-retinal antibodies in patients with age-related macular degeneration.

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in industrial counties. Recent findings indicate that the autoimmunity is involved in the pathogenesis of the disease. However, there is no autoantibody biomarker applied in a clinical setting for diagnosis and prognosis of AMD. In order to reveal retinal antigens targeted by serum IgG from AMD patients, mouse retinal tissue proteins were separated by 2-dimensional electrophoresis and the proteins in the immunoblots that were specific for dry and wet AMD patients IgG were identified by LC-MS/MS. Retinol-binding protein 3 and aldolase C (ALDOC) were mainly recognized by IgG form wet AMD patients. Pyruvate kinase M2 (PKM2) was targeted by both dry and wet AMD and level of anti-PKM2 IgG antibody was correlated best with the stage of AMD. Expression of ALDOC and PKM2 was decreased in mouse retina from aging whereas PKM2 deposit on RPE was increased in aged mice. Our data demonstrate that sera of AMD patients contain autoantibodies against retinal proteins and anti-PKM2 IgG serves as a biomarker for diagnosis and prognosis of AMD. Further investigation of the association of anti-retinal antibody level with expression level of antigens in retina will be needed to reveal the disease pathogenesis.

Serum autoantibody biomarkers for age-related macular degeneration and possible regulators of neovascularization.

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in industrial counties. Its pathogenesis is at least partially mediated by immunological factors, including a possible autoimmune response. To date, only a few antibodies have been identified in sera from patients with AMD. In order to reveal an autoantibody profile for AMD and identify biomarkers for progression of this disease, we have performed an antigen microarray analysis of serum samples from patients with AMD and healthy controls. Sera from the AMD groups contained high levels of IgG and IgM autoantibodies to some systemic antigens when compared to the normal group. Targeted antigens included cyclic nucleotide phosphodiesterase, phosphatidylserine (PS) and proliferating cell nuclear antigen. The IgG/IgM ratio for antibodies to PS was notably elevated in the AMD group compared to the normal group, and this ratio correlated best with the stage of AMD patients with an anti-PS ratio greater than the cut-off value had a 44-fold risk for advanced AMD with choroidal neovascularization. PS immunoreactivity was also elevated in AMD retina. Moreover, IgG autoantibodies purified from sera of AMD patients induced more tube formation on choroidal-retinal endothelial cells compared to those of healthy donors. Hence, sera from patients with AMD contain specific autoantibodies which may be used as biomarkers for AMD, and the IgG/M ratio for autoantibodies to PS might allow better monitoring of AMD progression.

Binocular Visual Function in a Pre-Presbyopic Patient with Uniocular Cataract Undergoing Cataract Surgery with a Multifocal Intraocular Lens.

BACKGROUND/AIM: An increasing number of pre-presbyopic patients are undergoing uniocular cataract extraction. We aim to compare the binocular status of subjects with uniocular cataracts, implanted either with a multifocal or a monofocal intraocular lens (IOL). MATERIALS AND METHODS: Subjects were recruited from outpatient ophthalmology clinics and randomized to an IOL type. Corrected and uncorrected LogMAR distance visual acuity (VA) and near and intermediate VA using the Radner reading test were completed. The binocular tests included the Worth Four Dot Test, fixation disparity, TNO stereoacuity and foveal suppression assessment. In addition to the near activity vision questionnaire. The trial was closed early because the chosen multifocal lens had been superseded by newer models. We report two subjects, one receiving the multifocal IOL and a monofocal IOL control with the most comparable baseline characteristics. RESULTS: Both subjects experienced uncomplicated cataract surgery, showing clinically significant improved corrected distance VA, 0.06 LogMAR and -0.16 LogMAR in the monofocal and multifocal IOL, respectively. The multifocal subject had 30 seconds of arc stereoacuity indicating normal binocular vision. Only gross binocular single vision with no stereopsis was found in the monofocal IOL subject. The latter subject also had reduced near vision quality-of-life questionnaire results. CONCLUSION: This two-patient case series demonstrates greater binocular near ability, with the multifocal IOL, in the pre-presbyopic patient undergoing uniocular cataract surgery. The case series highlights the need, and methodology for investigating further the functional and quality-of-life benefits of implanting multifocal IOLs in pre-presbyopic patients, those in their twenties and thirties, undergoing uniocular cataract surgery.

Anatomical and functional outcomes following switching from aflibercept to ranibizumab in neovascular age-related macular degeneration in Europe: SAFARI study.

BACKGROUND/AIMS: Prospective data on switching anti-vascular endothelial growth factors in patients with neovascular age-related macular degeneration (nAMD) who have previously shown no/partial response are limited. This prospective study assessed the effect of switching from aflibercept to ranibizumab on anatomical and functional outcomes in patients with persistent/recurrent disease activity. METHODS: SAFARI (NCT02161575) was a 6-month, prospective, single-arm study conducted in the UK and Germany. Patients, meeting strict eligibility criteria for one of two subgroups (primary treatment failure or suboptimal treatment response), received 3 monthly intravitreal ranibizumab injections (0.5 mg). Thereafter, ranibizumab was administered pro re nata at monthly visits. The primary endpoint was change from baseline (CfB) to day 90 in central subfield retinal thickness (CSRT). Best-corrected visual acuity (BCVA) and retinal morphology parameters were assessed. RESULTS: One hundred patients were enrolled (primary treatment failure, 1; suboptimal treatment response, 99). In the overall population, there was a significant CfB in median CSRT of -30.75 µm (95% CI -59.50,-20.50; p<0.0001) to day 90. Improvements were also observed in other quantitative and qualitative optical coherence tomography parameters. In Early Treatment Diabetic Retinopathy Study letters assessed by category, 55% and 59% of patients gained 0-≥15 letters versus baseline at day 90 and day 180, respectively. However, mean improvements in BCVA (CfB) to each time point were small (≤2 letters). No new safety signals were identified. CONCLUSION: Switching from aflibercept to ranibizumab led to a significant improvement in CSRT, with ~60% experiencing stabilised/improved BCVA. Therefore, patients with nAMD who have shown a suboptimal response to aflibercept may benefit from switching to ranibizumab.

Resource Use and Real-World Outcomes for Ranibizumab Treat and Extend for Neovascular Age-Related Macular Degeneration in the UK: Interim Results from TERRA.

INTRODUCTION: Ranibizumab is an inhibitor of vascular endothelial growth factor-A (anti-VEGF) approved for the treatment of neovascular age-related macular degeneration (nAMD). The treat and extend (T&E) regimen can potentially reduce the burden of clinic visits compared with a pro re nata (PRN) regimen. Retrospective, interim analyses of clinical effectiveness, treatment and resource use patterns were conducted using real-world data in England and Wales from the TERRA study. METHODS: Two cohorts, those switching from a PRN to a T&E regimen ('prior PRN') and those initiating ranibizumab on the T&E regimen as their first anti-VEGF therapy ('anti-VEGF-naïve') were enrolled in TERRA. Retrospective clinical assessments were gathered from medical records, while resource use patterns were collected via an operating cost questionnaire completed by each study site. RESULTS: At the interim analysis cut-off date (15 November 2016), 11 sites had enrolled 145 patients (prior PRN: n = 110; anti-VEGF-naïve: n = 35). Mean change from baseline (date of first injection) in visual acuity and central subfield retinal thickness to 12 months was +7.6 Early Treatment Diabetic Retinopathy Study letters [95% confidence interval (CI) 2.8, 12.4; p = 0.003; n = 27] and -67.7 µm (95% CI -106.5, -28.9; p = 0.001, n = 29), respectively, in the anti-VEGF-naïve cohort. Most T&E clinics were run as one-stop services (same-day monitoring and injection), whereas 4/10 PRN clinics were run as two-stop services (monitoring and injection on different days). In general, one-stop clinics used less staff resources and were likely to be shorter in duration for healthcare providers than the cumulative time spent for two-stop clinics. CONCLUSION: This is the first real-world observational study conducted in England and Wales demonstrating the effectiveness of the ranibizumab T&E regimen in anti-VEGF-naïve patients. T&E is compatible with one-stop clinic services, which these real-world data suggest to be less resource intensive than two-stop clinic services, possibly providing a dosing regimen beneficial to both patients and resource burden in UK clinical practice. FUNDING: Novartis Pharmaceuticals UK Limited.

In vivo demonstration of the anatomic differences between classic and occult choroidal neovascularization using optical coherence tomography.

PURPOSE: To determine architectural differences between classic and occult choroidal neovascularization (CNV) in vivo. DESIGN: Prospective observational case series. METHODS: Twenty-two patients with acute CNV underwent fluorescein angiography and optical coherence tomography (OCT), which were analyzed by separate blinded observers. RESULTS: In 87.5% of angiographically labeled "classic" CNV a discreet subretinal lesion corresponding to the neovascular complex could be seen above and separate to the retinal pigment epithelium on OCT. This was found in only 13.3% of "occult" CNV. CONCLUSION: With the latest commercially available OCT equipment it is now possible to confirm in vivo the previously proposed anatomic differences between fluorescein angiographically labeled classic and occult CNV. Classic CNV appear to grow predominantly in the subretinal space, whereas the majority of occult lesions do not. Optical coherence tomography features of CNV may correlate with response to photodynamic therapy or angiostatic treatments, as well as predicting the success of surgical removal.

Sensitivity and specificity of time-domain versus spectral-domain optical coherence tomography in diabetic macular edema.

PURPOSE: The purpose was to evaluate the sensitivity and specificity of measurements of central macular thickness (CMT) in diabetic macular edema using stratus time-domain and cirrus spectral-domain optical coherence tomography (OCT; Carl Zeiss Meditec, Dublin, CA). MATERIALS AND METHODS: A total of 36 eyes from 19 patients with clinically significant diabetic macular edema (DME) were included. All participants underwent automated scanning patterns using cirrus HD-OCT and stratus OCT examinations on the same day. The sensitivity/specificity of retinal thickness measurements was calculated from published normative data. Agreement was calculated using Bland--Altman method. The receiver operating characteristic curves (ROC) and areas under the ROC were plotted. RESULTS: The mean difference between the cirrus HD-OCT and stratus OCT in the central foveal zone was 49.89 µm. Bland--Altman analysis confirmed that the retinal thickness measurements had poor agreement in patients with DME. The areas under the ROC for retinal thickness measurements were 0.88 using cirrus HD-OCT and 0.94 with stratus. CONCLUSIONS: In patients with DME, the cirrus HD-OCT gives a higher reading than stratus OCT with poor agreement between the devices in most regions within the nine subfield zones. The sensitivity and specificity of the stratus OCT was comparable to the cirrus.

The effect of aqualase and phacoemulsification on the corneal endothelium.

PURPOSE: To compare corneal endothelial cell loss after cataract surgery by phacoemulsification and by Aqualase. METHODS: This was a prospective, randomized study of 75 eyes of 75 patients undergoing cataract surgery. Patients were randomly assigned to receive either phacoemulsification or Aqualase for cataract removal. Specular microscopy was used to calculate endothelial cell counts preoperatively and 3 weeks and 6 months afterwards. Best-corrected visual acuity was also measured. The t-test was used to detect statistical significance. RESULTS: The mean endothelial cell loss was 8.1% in the phacoemulsification group and 6.8% in the Aqualase group. There was no statistically significant difference in the amount of endothelial cell loss or in visual outcome between the 2 groups. The number of Aqualase pulses tended to increase with nuclear density while the phacoemulsification time showed little variation with nuclear subtype. CONCLUSION: Endothelial cell loss after cataract surgery is similar whether phacoemulsification or Aqualase is used. Aqualase can be considered to be as safe as phacoemulsification with regard to corneal trauma and is a useful alternative especially for soft cataracts.

Targeting leukostasis for the treatment of early diabetic retinopathy.

Leukocyte-endothelial interaction plays an important role in the early phase of the development of diabetic retinopathy. It has been studied extensively linking inflammatory processes to its development conducted to date in rats and mice, and have focused on insulin-deficient models. The molecular and functional changes that are characteristics of inflammation have been detected in retinas from diabetic animals and humans with involvement of multiple pathways that results in the final sequelae of increased permeability of the blood retinal barrier and finally ischemia that drives angiogenesis. Increased expression of Intracellular adhesion molecules heralds the onset of changes that results in attraction of leucocytes such as neutrophils. The consequent release of cytokines and growth factors such as vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha, and interleukin 1-Beta results in increased permeability and retinal edema. Other indirect mediators involved include pathways such as the protein kinase C (PKC), renin-angiotensin system, enzymes such as the poly ADP-ribose polymerase, 3-hydroxy-3-methylglutaryl-coenzyme A reductase, nitric oxide synthetase and finally advanced glycation products. Therapy for early diabetic retinopathy may inhibit one or more of these pathways using drugs that can be given systemically, with local ocular applications having a more direct effect as in other eye diseases.

Macular and retinal dysfunction of unknown origin in adults with normal fundi: evidence for an autoimmune pathophysiology.

Here we report the discovery of and phenotypic characterization of a retinal disorder of unknown origin in adults using clinical, electrophysiological and psychophysical techniques, and to seek the presence of circulating retinal autoantibodies in the sera of these patients. Sixteen patients were identified with progressive bilateral visual loss over a period of months. Ten of the patients were male, and the average age was 55.3 years (range from 43 to 76 years). Known causes such as carcinoma-associated retinopathy, acute zonal occult outer retinopathy and hereditary cone dystrophy appeared unlikely. Investigations included electrophysiology, fundus autofluorescence imaging and psychophysical tests. The sera of these patients were analyzed with indirect immunocytochemistry and Western immunoblot analysis on murine (BALB/c) retinal tissue for the presence of retinal autoantibodies. Bilateral visual loss and photophobia progressed over a period of months to years (average 28.7 months, range 3-67) and subsequently stabilized. No abnormality was observed by biomicroscopy, angiography or autofluorescence imaging. Electrophysiology indicated predominant cone-system dysfunction, either macular or generalized, and post-phototransduction involvement in 9 patients (56%). Photopic and scotopic visual fields and dark adaptation kinetics showed both cone and rod system involvement in all cases. Heterogeneous immunohistochemical staining patterns were seen with the sera of these patients as compared with controls. A majority of the affected patients (9/15) stained with an antinuclear pattern. The retinal autoantibodies from the sera of most patients reacted with the retinal proteins of molecular weight between 34 and 40 kDa. The aetiology of this distinctive retinal disorder therefore appears to be mediated through an autoimmune mechanism.