Atrophy in Neovascular Age-Related Macular Degeneration: Age-Related Eye Disease Study 2 Report Number 15.

PURPOSE: To identify the development and progression of macular retinal pigment epithelial atrophy in eyes with neovascular (CNV) age-related macular degeneration (AMD) and to correlate with visual acuity (VA). DESIGN: Cohort study. PARTICIPANTS: Age-Related Eye Disease Study 2 (AREDS2) participants with intermediate AMD enrolled in a randomized controlled clinical trial of oral supplements. Analyses were conducted in the subset of AREDS2 participants who were also enrolled in the fundus autofluorescence ancillary (FAF) ancillary study. METHODS: Color photographs and FAF images were evaluated in eyes that developed CNV. Presence of geographic atrophy (GA) prior to the incidence of CNV and the development of macular atrophy following incident CNV were assessed. Areas of hypoautofluorescence representing atrophy were measured for area and macular involvement. Enlargement rate of atrophy and change in visual acuity over time were analyzed. MAIN OUTCOME MEASURES: incidence and enlargement rate of atrophy and VA changes in eyes with incident CNV. RESULTS: Incident CNV developed in 334 (9.2%) of eyes evaluated in the AREDS2 FAF substudy. Of these, 40% had macular atrophy at incidence of CNV with half of these attributable to pre-existing GA. Atrophy developed in 14.7 % of eyes over 4 years of follow-up. Mean area of atrophy was largest in eyes with pre-existing GA and CNV (5.17 mm2, p<0.001), and atrophy involved the center of the macula in > 65% of eyes. Mean VA letter score at the annual visit in which CNV was documented was similar in the three groups with atrophy; eyes with CNV and pre-existing GA, incident atrophy at the first visit with CNV, and atrophy during follow up (60 letters). Enlargement rate of atrophy was also similar in eyes in the three groups (1.23 - 1.86 mm2, p = 0.47). Eyes with macular atrophy lost more visual acuity compared to eyes without atrophy, particularly after 2 years of follow-up (-10.9 vs. - 3.6 letters, p = 0.07). CONCLUSION: Atrophy is commonly seen in neovascular AMD and often can be attributed to pre-existing GA. Macular atrophy and GA appear to be a continuum of the same disease process and are both associated with poor vision.

Differences in the auxological characters of children with short stature - Differential diagnostic possibilities of hypothyreosis.

This study aimed to define the differences in growth characteristics in the three most frequent causes of growth retardation - growth hormone deficiency, hypothyreosis and constitutional delay of growth and development - in order to provide diagnostic means for distinguishing these disorders. The study included 166 children with growth disorders aged 4-18 years. The height for age, the bone age using the TW3 method, the predicted height as the target height and the current prediction using the TW3 method were studied. For bone age, the radius, ulna and short bones compartment (RUS) and carpal bones (CARP) were evaluated separately and the difference in their delay in relation to chronological age (ΔBA_RUS_CARP) was determined. The relationship of the studied variables with sex and the underlying diagnosis was tested and the relationship of hypothyreosis and growth data was estimated. The model was tested on the growth data of 104 randomly selected patients with a growth disorder. The largest significant distinction was demonstrated by the difference ΔBA_RUS_CARP in hypothyreosis. The created linear regression model was highly statistically significant (χ2 = 19.4, p < 0.0001) and showed high selectivity (0.609, 95% CI 0.409; 0.808) as well as high specificity (0.864, 95% CI 0.781; 0.946). The clinical validity of the model demonstrated a 61% predictive value for the detection and an 81% successful specification of hypothyreosis. The study demonstrated the possibility of distinguishing suspected hypothyreosis from other causes of growth retardation based on differences in severity of the ossification delay in skeletal compartments of the hand.

Metabotropic Glutamate 2/3 Receptors and Epigenetic Modifications in Psychotic Disorders: A Review.

Schizophrenia and Bipolar Disorder are chronic psychiatric disorders, both considered as "major psychosis"; they are thought to share some pathogenetic factors involving a dysfunctional gene x environment interaction. Alterations in the glutamatergic transmission have been suggested to be involved in the pathogenesis of psychosis. Our group developed an epigenetic model of schizophrenia originated by Prenatal Restraint Stress (PRS) paradigm in mice. PRS mice developed some behavioral alterations observed in schizophrenic patients and classic animal models of schizophrenia, i.e. deficits in social interaction, locomotor activity and prepulse inhibition. They also showed specific changes in promoter DNA methylation activity of genes related to schizophrenia such as reelin, BDNF and GAD67, and altered expression and function of mGlu2/3 receptors in the frontal cortex. Interestingly, behavioral and molecular alterations were reversed by treatment with mGlu2/3 agonists. Based on these findings, we speculate that pharmacological modulation of these receptors could have a great impact on early phase treatment of psychosis together with the possibility to modulate specific epigenetic key protein involved in the development of psychosis. In this review, we will discuss in more details the specific features of the PRS mice as a suitable epigenetic model for major psychosis. We will then focus on key proteins of chromatin remodeling machinery as potential target for new pharmacological treatment through the activation of metabotropic glutamate receptors.

Association of outer retinal layer morphology with visual acuity in patients with retinal vein occlusion: SCORE Study Report 13.

PURPOSE: To assess associations between visual acuity (VA) and the status of the photoreceptor inner segment-outer segment (IS-OS) junction in a subset of patients in the Standard Care vs COrticosteroid for REtinal Vein Occlusion (SCORE) Study. METHODOLOGY: High-resolution time domain optical coherence tomography (OCT) scans of study eyes from a single site participating in the SCORE Study were evaluated. Integrity of the IS-OS junction in the central subfield was evaluated using a three-step scale: absent, abnormal or normal. Associations of the IS-OS status with ETDRS VA letter score and center point thickness (CPT) were investigated. RESULTS: Baseline OCTs of 42 eyes were evaluated. The IS-OS junction was absent in 30 (71%) and abnormal in 12 (29%). At month 12, the IS-OS junction was absent in 18 (43%), abnormal in 12 (28%), and normal in 12 (28%) eyes. At baseline, IS-OS status was significantly associated with CPT, but not with VA. At month 12, IS-OS status was significantly associated with CPT and VA, that is, absent or abnormal IS-OS was associated with increased CPT and worse VA. Change in IS-OS status was not associated with change in CPT (P=0.8). Worsening of IS-OS status was associated with loss of VA and improvement in IS-OS status to normal was associated with gain in VA (P=0.03). CONCLUSION: In this data set with long-term follow-up of OCTs as part of the SCORE Study, there is a correlation between change in IS-OS status and VA. This supports further evaluation of outer retinal morphology in larger data sets.

Anticardiolipin antibodies in hemodialysis patients with hepatitis C and their role in fistula failure.

BACKGROUND/AIMS: Several conflicting results are presently reported regarding raised IgG and IgM-anticardiolipin antibodies (ACA) titers in hemodialysis (HD) patients and their role in vascular access dysfunction. We aimed to determine the prevalence of both IgM and IgG-ACA titers and to analyze retrospectively their role in primary and secondary arteriovenous fistula (AVF) failure in a homogeneous group of HD patients with chronic hepatitis C. METHODS: This study included 103 adults on maintenance hemodialysis with chronic hepatitis C infection. All participants had blood samples drawn predialysis and after an overnight fast. Analysis included biochemistry, IgG and IgM ACA, Anti-HCV, HBsAg, serum HCV RNA and HCV genotyping. RESULTS: The prevalence of IgG-ACA was 14.6% (15/103). No patient had a positive value of the IgM-ACA test. HCV replication was detected in 52 of 76 patients. The most common HCV genotype was genotype 1 (90%). The percentage of females was higher in ACA(+) group (p = 0.038). There were no significant differences between subjects with and without ACA-IgG regarding other parameters studied. No difference in regard to AVF survival was detected between ACA(+) and ACA(-) groups (p > 0.05). CONCLUSION: We found no significant differences in primary or secondary AVF failure between patients with elevated and normal ACA. Therefore, we conclude that AVFF may be caused by factors other than ACA in these patients. More prospective studies are needed to confirm this observation.

Sustained moderate visual loss as a predictive end point for visual loss in non-proliferative diabetic retinopathy.

PURPOSE: In PKC-DRS2, the efficacy of the oral PKC-beta inhibitor, ruboxistaurin 32 mg/day, was measured by the primary end point of sustained moderate visual loss (SMVL: a > or = 15 letter decrease from baseline on the ETDRS (Early Treatment Diabetic Retinopathy Study) chart sustained at least for the last 6 months of study participation). We now evaluate whether SMVL is more accurate than moderate visual loss (MVL: a single occurrence of a decrease from baseline of > or = 15 ETDRS letters) for predicting future visual loss. METHODS: Study eyes with moderately severe to very-severe non-proliferative diabetic retinopathy, best-corrected visual acuity of at least 45 letters on the ETDRS chart (approximately Snellen 20/125), and no prior pan retinal photocoagulation were evaluated in 506 patients (869 eyes) who completed 36 months of treatment. RESULTS: Sixty-five percentage (26/40) of study eyes with the onset of SMVL within 24 months of enrolment still had SMVL at study completion (36 months). In comparison, only 24% (30/126) with MVL within 24 months had SMVL at study completion. Analyses based on data from 6, 12, and 18 months of treatment were similar. CONCLUSIONS: SMVL is a more predictable measure of subsequent visual loss than is a single time point measure of MVL.

Does the direction of arterial needle in AV fistula cannulation affect dialysis adequacy?

AIM: The direction of arterial access needles in fistulas and grafts has been a subject of some controversy and there is no study comparing the results either direction of arterial needle placement in cannulation of arteriovenous fistula. We compared mean urea reduction rate (URR) and Kt/V in the same HD patients when dialyzed via antegrade or retrograde arterial needle cannulation. MATERIALS AND METHODS: This was a study involving 22 adults on maintenance hemodialysis for more than 6 months. Doppler US examinations of arteriovenous fistula were performed in all subjects. Pre-dialysis and post-dialysis blood samples were obtained at the patient's midweek HD treatment 4 times a month for each direction. Arterial needle was placed in retrograde direction for the first month. On the second month, the direction of arterial needle was converted to antegrade. Means were compared by paired t-test. RESULTS: Mean URR and eKt/Vof retrograde cannulation were 74.2+/-7.2% and 1.57+/-0.33. The results were indifferent statistically from those of antegrade cannulation (73.0+/-8.7% and 1.57+/-0.35 (p=0.123)). Mean fistula blood flow was 931 +/- 483 ml/min. No cannulation complication was observed during the study period for both directions. CONCLUSIONS: Both antegrade and retrograde arterial needle placement may be preferred according to center experience without concern of HD adequacy. Longterm outcomes of antegrade and retrograde arterial needle placement such as AVF failure, thrombosis, and stenosis warrant further studies.

Clinical significance of elevated antinuclear antibody test in patients with Hodgkin's and Non-Hodgkin's lymphoma: a single center experience.

AIM: There is an increased risk of lymphoma subsequent to autoimmune conditions. Autoimmune disorders may occur in the course of lymphomas. In this study, the association of autoimmunity and related autoantibodies within non-Hodgkin's (NHL) and Hodgkin's lymphoma (HL) patients has been investigated. METHODS: The study enrolled 119 patients affected by NHL and 60 patients affected by HL for the presence of autoantibodies and autoimmune diseases. Afterwards, the results between the two lymphoma groups have been confronted. RESULTS: Autoimmune diseases were diagnosed in eight (6.7%) patients with NHL and three patients with HL (5%) (P=0.651). Thirty-four (28.5%) patients with NHL and 14 (23.3%) patients with HL displayed autoantibody positivity (P=0.083). As regards HL cases, antinuclear antibodies (ANA) were detected in 12 (20%) and anti PM-Scl in two patients (3.3%). None the patients had anti Jo-1, anti Scl-70, anti Sm, anti nRNP/Sm, anti single-stranded DNA (anti-ssDNA), anti double-stranded DNA (anti-dsDNA), antihistones, antinucleosomes, anti SS-A, anti SS-B or anti CENP-B autoantibodies. In patients affected by NHL ANA was detected in 16 (13.4%), anti SS-A and anti SS-B in two (1.7%), anti CENP-B in eight (6.7%) and anti PM-Scl in eight patients (6.7%). None of the patients had anti Jo-1, anti Scl-70, anti Sm, anti nRNP/Sm, anti ssDNA, antihistones or antinucleosome antibodies. There was a statistically significant difference between patients with HL and NHL in terms of anti CENP-B positivity (P=0.040). CONCLUSION: In conclusion, ANA and related autoantibodies can frequently be detected during lymphoma treatment. However, the majority of lymphoma patients with positive ANA did not display autoimmune diseases, demonstrating the lack of a strict correlation between the presence of ANA and autoimmune diseases.

Randomized trial of peribulbar triamcinolone acetonide with and without focal photocoagulation for mild diabetic macular edema: a pilot study.

OBJECTIVE: To provide pilot data on the safety and efficacy of anterior and posterior sub-Tenon injections of triamcinolone either alone or in combination with focal photocoagulation in the treatment of mild diabetic macular edema (DME). DESIGN: Prospective, phase II, multicenter, randomized clinical trial. PARTICIPANTS: One hundred nine patients (129 eyes) with mild DME and visual acuity 20/40 or better. METHODS: The participants were assigned randomly to receive either focal photocoagulation (n = 38), a 20-mg anterior sub-Tenon injection of triamcinolone (n = 23), a 20-mg anterior sub-Tenon injection followed by focal photocoagulation after 4 weeks (n = 25), a 40-mg posterior sub-Tenon injection of triamcinolone (n = 21), or a 40-mg posterior sub-Tenon injection followed by focal photocoagulation after 4 weeks (n = 22). Follow-up visits were performed at 4, 8, 17, and 34 weeks. MAIN OUTCOME MEASURES: Change in visual acuity and retinal thickness measured with optical coherence tomography (OCT). RESULTS: At baseline, mean visual acuity in the study eyes was 20/25 and mean OCT central subfield thickness was 328 mum. Changes in retinal thickening and in visual acuity were not significantly different among the 5 groups at 34 weeks (P = 0.46 and P = 0.94, respectively). There was a suggestion of a greater proportion of eyes having a central subfield thickness less than 250 mum at 17 weeks when the peribulbar triamcinolone was combined with focal photocoagulation. Elevated intraocular pressure and ptosis were adverse effects attributable to the injections. CONCLUSIONS: In cases of DME with good visual acuity, peribulbar triamcinolone, with or without focal photocoagulation, is unlikely to be of substantial benefit. Based on these results, a phase III trial to evaluate the benefit of these treatments for mild DME is not warranted.

Parathyroid hormone as a marker for the differential diagnosis of acute and chronic renal failure.

It is often difficult to distinguish acute renal failure clinically from chronic renal failure, especially in patients who do not have records of their medical history. We investigated the magnitude of iPTH increase in ARF and the potential role of iPTH as a marker for differential diagnosis of ARF and CRF in new patients referred to our renal unit. We prospectively analyzed 122 (ARF n = 64, CRF n = 58) patients referred to our renal unit with serum creatinine higher than 2 mg/dL. ROC curve analysis was performed to investigate role of iPTH for differentiating ARF from CRF. The sensitivity, specificity, and positive predictive value of iPTH in discrimination of ARF and CRF were calculated. There was no statistically significant difference regarding the means of age, sex distribution, and serum chemistry between patients with ARF or CRF. But serum iPTH (p < 0.0001) levels were lower in patients with ARF than in those with CRF. A cutoff, set at 170 pg/mL for iPTH to discriminate patients with CRF, yielded a sensitivity of 88% and a specificity of 89%. This study confirms that the iPTH measurement is of clinical value in differentiating acute from chronic renal failure.

Intravitreal triamcinolone with photodynamic therapy for subfoveal choroidal neovascularisation in age related macular degeneration.

AIMS: To report the effects of intravitreal triamcinolone acetonide (iTAAC) injections as an adjunctive treatment to photodynamic therapy (PDT) with verteporfin for new subfoveal choroidal neovascularisation (CNV) in age related macular degeneration (AMD). METHODS: We retrospectively reviewed the records of all AMD patients who had iTAAC within 6 weeks of their first PDT and had a follow up of one year or longer. The proportion of eyes after one year follow up that lost or gained >or=15 and >or=30 ETDRS letters, baseline and one year lesion greatest linear dimension (GLD), number of PDTs, and side effects were assessed. RESULTS: Fourteen patients were evaluated. Eleven received one initial combined treatment and three received an additional combined treatment after 6 months. Median follow up was 18 months (range 12 to 25 months). Overall, 7% gained >or=30 letters, 50% maintained stable vision, 14% lost 15-29 letters, and 29% lost >or=30 letters. Overall, mean GLD increased from 2580 (SD 1088) microm to 3946 (SD 1503) micro m (p = 0.01). The mean number of PDTs during the first year was 2.57. Side effects were mild intraocular pressure elevation in 28.5% and cataract progression in 50% of phakic eyes. CONCLUSIONS: iTAAC with PDT in AMD was found to be relatively safe and had reasonable results for lesions with some classic component.

Choroidal neovascular membrane inhibition in a laser treated rat model with intraocular sustained release triamcinolone acetonide microimplants.

AIM: To determine if intravitreal microimplants containing triamcinolone acetonide (TAAC) inhibit experimental fibrovascular proliferation (FVP) induced by laser trauma in a rat as a model of choroidal neovascular membranes (CNVMs). METHODS: 20 anaesthetised male Brown Norway rats received a series of eight krypton red laser lesions per eye (647 nm, 0.05 s, 50 micro m, 150 mW). Three types of sterilised TAAC microimplant designs were evaluated: implant A consisting of 8.62% TAAC/20% polyvinyl alcohol (PVA) matrix (by dry weight); implant B consisting of 3.62% TAAC/20% PVA matrix; and implant C consisting of a dual 8.62% TAAC/20% PVA matrix design combined with a central core (0.5 mm) of compressed TAAC to extend the implant release time. For each animal studied, one eye received one of the three aforementioned TAAC implant designs, while the fellow eye received a control implant consisting of PVA but without TAAC. The animals were sacrificed at day 35 and ocular tissues were processed for histological analysis. Serial histological specimens were methodically assessed in a masked fashion to analyse each laser lesion for the presence or absence of FVP; maximum FVP thickness for each lesion was measured from the choriocapillaris. RESULTS: All three types of TAAC implants inhibited FVP relative to controls in a statistically significant fashion. In the eyes that received implant A (n = 8), the mean thickness of the recovered lesions (n = 36) measured 32 (SD 22) micro m, compared to 52 (30) micro m (p <0.005) for the recovered lesions (n = 40) from the fellow control eyes. In the eyes that received implant B (n = 6), the mean thickness of the recovered lesions (n = 31) measured 28 (15) micro m, compared to 50 (29) micro m (p <0.001) for the lesions (n = 19) recovered from the fellow control eyes. In the eyes that received implant C (n = 6), the mean thickness of the recovered lesions (n = 21) measured 39 (24) micro m, compared to 65 (30) micro m (p <0.001) for the lesions (n = 39) recovered from the fellow control eyes. CONCLUSIONS: All three of the tested TAAC microimplant designs produced potent inhibition of FVP in a rat model of CNVMs. There were no differences in inhibition of FVP between the three different types of implants evaluated. This study provides evidence that: (1) corroborates previous investigations that propose TAAC as a potential treatment for CNVMs in humans, and (2) demonstrates TAAC can be effectively delivered via long acting sustained release intraocular microimplants. It should be noted, however, that the FVP observed in this rat laser trauma may not reflect the CNVM observed in human with exudative age related macular degeneration (AMD).

Intravitreal triamcinolone in subfoveal recurrence of choroidal neovascularisation after laser treatment in macular degeneration.

BACKGROUND: Laser treatment of extrafoveal well delineated choroidal neovascularisation in exudative age related macular degeneration has a high rate of failure with subsequent severe vision loss from subfoveal involvement. Laser treatment may limit scotoma size, but is unpalatable because of early persistent vision loss. Intravitreal triamacinolone injection may be an acceptable alternative therapy in such disparate cases. METHODS: 14 consecutive patients with recurrent neovascularisation were treated with a single 4.0 mg injection of triamacinolone and followed for up to 1 year. Visual results were compared with published data from the Macular Photocoagulation Study of recurrent neovascularisation. RESULTS: Mean visual acuity remained stable at about 20/200 throughout the study period in the treated patients. This is comparable to the outcomes in the Macular Photocoagulation Study for laser retreated patients, and better than the observation group. CONCLUSIONS: Intravitreal triamcinolone may be an acceptable treatment of subfoveal recurrent neovascularisation while avoiding early persistent vision loss from laser retreatment.

Transpupillary thermotherapy for subfoveal occult choroidal neovascularization: effect on ocular perfusion.

PURPOSE: To perform a descriptive analysis of the effects on ocular blood flow of transpupillary thermotherapy (TTT) for occult subfoveal choroidal neovascular membranes (CNVMs) in age-related macular degeneration (AMD). METHODS: Eleven subjects with occult subfoveal CNVM due to AMD were assessed in a masked fashion by color Doppler imaging (CDI) within 24 hours before, 24 hours after, and 1 month after undergoing TTT. RESULTS: In the posterior ciliary arteries (PCAs), there were no statistically significant changes observed in the peak systolic velocity (PSV), end diastolic velocity (EDV), or resistive index (RI) at 24 hours. At 1 month, the mean EDV decreased 36% (P = 0.0105) and the mean RI increased 3.8% (P = 0.0305) in the nasal PCA. Although there was a similar trend in the temporal PCA, the differences did not reach statistical significance. In the central retinal artery (CRA), the mean PSV decreased 16% (P = 0.0137), and the mean EDV decreased 21% (P = 0.0222) at 24 hours after treatment. There were no statistically significant differences in the CRA blood flow indices at 1 month after treatment. In the ophthalmic artery, there were no statistically significant differences observed in the mean PSV, EDV, or RI at 24 hours or 1 month after treatment. CONCLUSIONS: TTT is associated with transiently decreased volumetric blood flow in the retinal circulation 24 hours after treatment. In the posterior ciliary arteries that supply the choroid, there were no changes observed at 24 hours, but at 1 month, there was a decrease in the mean EDV and an increase in the RI in the nasal and temporal PCAs, reaching statistical significance in the nasal PCA only. This study suggests that TTT could lead to alterations in choroidal blood flow, as assessed by CDI. Further study is warranted.

Relation between dietary intake, serum concentrations, and retinal concentrations of lutein and zeaxanthin in adults in a Midwest population.

BACKGROUND: Information on concentrations of retinal carotenoids (macular pigment, or MP) is of particular interest because MP protects against age-related macular degeneration, the leading cause of irreversible blindness in the United States. OBJECTIVE: This study was designed to evaluate the relation between dietary intake, blood concentrations, and retinal concentrations of carotenoids in a large group of volunteers. DESIGN: Two hundred eighty volunteers in the Indianapolis area completed health and diet questionnaires, donated a blood sample, and participated in MP density assessment to determine retinal carotenoid status. Dietary intake was assessed by food-frequency questionnaire. Serum concentrations of lutein, zeaxanthin, and beta-carotene were measured by HPLC. MP optical density (MPOD) was determined psychophysically with a 460-nm, 1 degrees test stimulus. RESULTS: Average MPOD was 0.21 +/- 0.13. Average intakes of lutein + zeaxanthin and beta-carotene were 1101 +/- 838 and 2935 +/- 2698 microg/d, respectively. Although several key dietary intake variables (eg, lutein + zeaxanthin and beta-carotene) differed by sex, no significant sex differences were found in either serum concentrations of lutein and zeaxanthin or MPOD. Serum beta-carotene concentrations were significantly higher in women than in men. Serum lutein + zeaxanthin and dietary intake of lutein + zeaxanthin were significantly correlated and significantly related to variations in MPOD (r = 0.21, P < 0.001, and r = 0.25, P < 0.001, respectively). CONCLUSIONS: Retinal carotenoids can be measured in epidemiologic studies. In this study, MPOD was associated with lutein + zeaxanthin in the diet and the serum. Retinal concentrations, however, were influenced by other factors as well. To understand the effect of dietary lutein + zeaxanthin intake on the retina and risk of age-related eye disease, future studies should include measures of macular concentrations of these pigments.

Potential therapeutic application of antisense oligonucleotides in the treatment of ocular diseases.

Antisense oligonucleotides are a class of compounds being developed as therapeutic agents for many types of diseases. Although still relatively early in the clinical characterisation, the power of this technology lies in the ability to utilise genetic information and the known molecular mechanisms of disease to foster efficient and rational drug design. Consideration of novel approaches to treating ocular diseases is of interest because there are many ocular diseases with no satisfactory treatments. The recent availability of animal models of many ocular diseases provides the opportunity to use antisense oligonucleotides to understand the mechanisms of disease pathology and to potentially intervene therapeutically in ocular disease. There are already a number of examples where antisense oligonucleotides have been applied to the study of ocular physiology and disease and there is an antisense oligonucleotide approved for the treatment of cytomegalovirus (CMV) retinitis. We summarise current research in this area and highlight the properties of these compounds that are favourable for use as ocular therapeutics.

Anti-angiogenic therapy of proliferative diabetic retinopathy.

Proliferative diabetic retinopathy (PDR) remains one of the major causes of acquired blindness in developed nations. This is true despite the development of laser treatment, which can prevent blindness in the majority of those who develop this complication. The hallmark of PDR is neovascularisation (NV), abnormal angiogenesis that may ultimately cause severe vitreous cavity bleeding and/or retinal detachment. Pharmacologic therapy aimed at preventing NV, as an adjunct to laser treatment, or as an alternative to laser treatment, would be a welcome addition to the armamentarium. PDR could be prevented by improved metabolic control or by pharmacologically blunting the biochemical consequences of hyperglycaemia (e.g., with aldose reductase inhibitors, inhibitors of non-enzymatic glycation or by protein kinase C (PKC) inhibition). The angiogenesis in PDR could be treated via growth factor (e.g., vascular endothelial growth factor (VEGF), insulin like growth factor-1) blockade, integrin (e.g., alpha-v beta-3) blockade or extracellular matrix alteration (e.g., with steroid compounds), or interference with intracellular signal transduction pathways (e.g., PKC and mitogen activated protein kinase pathway proteins). Numerous potentially useful anti-angiogenic compounds are in development, but two drugs are presently in clinical trials for the treatment of the preproliferative stage of PDR.