Intravitreal conbercept as an adjuvant in vitrectomy for proliferative diabetic retinopathy: a meta-analysis of randomised controlled trials.

PURPOSE: To evaluate the efficacy of intravitreal conbercept (IVC) in pars plana vitrectomy (PPV) for patients with proliferative diabetic retinopathy (PDR). METHODS: A meta-analysis of randomized control trials (RCTs) using online databases was performed. The intraoperative outcome measures were the incidence of intraoperative bleeding and endodiathermy application, and the mean surgical time. The postoperative outcome measures were mean change in best-corrected visual acuity (BCVA) from baseline, postoperative vitreous clear-up time and incidence of recurrent vitreous hemorrhage (VH). RESULTS: Eight RCTs were selected for meta-analysis. They included 409 eyes (215 eyes in IVC group and 194 eyes in no conbercept group). Preoperative IVC application was associated with less intraoperative bleeding and endodiathermy applications (RR = 0.34, 95% CI, 0.23-0.50, P < 0.00001, and RR = 0.26, 95% CI, 0.12-0.56, P = 0.0005) compared to no conbercept. It also shortened surgical time (WMD = -15.87, 95% CI, -22.04 to -9.69, P < 0.00001). In addition, preoperative or intraoperative IVC achieved better BCVA outcome (WMD = -0.37, 95% CI, -0.62 to -0.13, P = 0.003), shorter vitreous clear-up time postoperatively (WMD = -5.44, 95% CI, -6.31 to -4.57, P < 0.00001) and a lower rate of VH recurrence (RR = 0.45, 95% CI, 0.22-0.91, P = 0.03). CONCLUSION: IVC is an effective adjuvant in PPV for PDR, with better intraoperative and postoperative outcomes.

Iatrogenic retinal breaks and postoperative retinal detachments in microincision vitrectomy surgery compared with conventional 20-gauge vitrectomy: a meta-analysis.

PURPOSE: To assess the incidence of iatrogenic retinal breaks (IRBs) and postoperative retinal detachments (RDs) in microincision vitrectomy surgery (MIVS) compared with 20-gauge (20 G) vitrectomy. METHODS: A comprehensive literature search was performed to find relevant studies and a meta-analysis of the IRBs and postoperative RDs rates after 20 G vitrectomy versus MIVS was conducted. RESULTS: Thirty-two studies were selected, including 14,373 eyes (6932 eyes in the 20 G group, 7441 eyes in the MIVS group). The meta-analysis demonstrated that the incidence of IRBs was significantly higher in 20 G vitrectomy vs. MIVS (OR = 2.22, 95% CI, 1.93-2.57, P < 0.00001) and in a subanalysis vs. 23 G MIVS (OR = 2.19, 95% CI, 1.87-2.56, P < 0.00001) and vs. 25 G MIVS (OR = 2.27, 95% CI, 1.62-3.18, P < 0.00001). Similar result was obtained in a subanalysis for macular surgery (OR = 2.44, 95% CI, 1.99-2.99, P < 0.00001), and also for sclerotomy-related IRBs (OR = 3.73, 95% CI, 2.55-5.44, P < 0.00001), but not for surgically induced posterior vitreous detachment-related IRBs (OR = 1.59, 95% CI, 0.89-2.84, P = 0.12). The incidence of postoperative RDs in 20 G vitrectomy was significantly higher compared to MIVS (OR = 1.72, 95% CI, 1.21-2.46, P = 0.003) and in a subanalysis vs. 23 G MIVS (OR = 2.45, 95% CI, 1.50-4.00, P = 0.0003), but not for 25 G MIVS (OR = 1.01, 95% CI, 0.63-1.64, P = 0.96). Similar result was obtained in a subanalysis for macular surgery (OR = 1.89, 95% CI, 1.26-2.85, P = 0.002). CONCLUSION: This meta-analysis demonstrated that MIVS is associated with a lower risk of IRBs and postoperative RDs compared to 20 G vitrectomy.

Therapeutic potential of valproic acid for retinitis pigmentosa.

BACKGROUND/AIM: To examine the efficacy and safety of valproic acid (VPA) in patients with retinitis pigmentosa (RP). METHODS: Thirteen eyes were examined before and after brief treatment (average 4 months) with VPA. Visual fields (VF) for each eye were defined using digitised Goldmann Kinetic Perimetry tracings. VF areas were log-transformed and VF loss/gain relative to baseline was calculated. Visual acuity was measured using a Snellen chart at a distance of 20 feet (6.1 m). Values were converted to the logarithm of the minimum angle of resolution (logMAR) score. RESULTS: Nine eyes had improved VF with treatment, two eyes had decreased VF and two eyes experienced no change, with an overall average increase of 11%. Assuming typical loss in VF area without treatment, this increase in VF was statistically significant (p<0.02). An average decrease (0.172) in the logMAR scores was seen in these 13 eyes, which translates to a positive change in Snellen score of approximately 20/47 to 20/32, which was significant (p<0.02) assuming no loss in acuity without treatment. Side effects were mild and well tolerated. CONCLUSION: Treatment with VPA is suggestive of a therapeutic benefit to patients with RP. A placebo-controlled clinical trial will be necessary to assess the efficacy and safety of VPA for RP rigorously.

Delayed dark-adaptation and lipofuscin accumulation in abcr+/- mice: implications for involvement of ABCR in age-related macular degeneration.

PURPOSE: To examine the ocular phenotype in mice heterozygous for a null mutation in the abcr gene. METHODS: Retinas and retinal pigment epithelia (RPE) were prepared from wild-type, abcr+/-, and abcr-/- mice. Fresh tissues were homogenized and analyzed by normal phase high-performance liquid chromatography (HPLC) for the presence of retinoids and phospholipids. In another study, fixed tissues were sectioned and analyzed by light and electron microscopy. Finally, anesthetized mice were studied by electroretinography (ERG) at different times after exposure to strong light. RESULTS: A2E, the major fluorophore of lipofuscin, and its precursors, A2PE-H(2) and A2PE, were approximately fourfold more abundant in 8-month-old abcr+/- than in the wild-type retina and RPE. The levels of these substances in abcr+/- mice were approximately 40% those in abcr-/- mice. Lipofuscin pigment-granules were also visible in abcr+/- RPE cells by electron microscopy. Accumulation of A2PE-H(2) and A2E in abcr+/- retina and RPE, respectively, was strongly dependent on light exposure. Heterozygous mutants also exhibited delayed recovery of rod sensitivity by ERG. This delay was correlated with elevated levels of all-trans-retinaldehyde (all-trans-RAL) in retina after a photobleach and was not caused by a reduction in quantum-catch due to depletion of 11-cis-retinaldehyde (11-cis-RAL). CONCLUSIONS: Partial loss of the ABCR or rim protein is sufficient to cause a phenotype in mice similar to recessive Stargardt's disease (STGD) and age-related macular degeneration (AMD) in humans. These data are consistent with the suggestion that the STGD carrier-state may predispose to the development of AMD.

Autosomal dominant retinal degeneration and bone loss in patients with a 12-bp deletion in the CRX gene.

PURPOSE: To define the phenotypic expression of a deletion in the gene encoding the transcription factor CRX in a large, seven-generation, white family. METHODS: Fourteen affected individuals, all heterozygous for the Leu146del12 mutation in the cone-rod homeobox gene (CRX), and four nonaffected relatives from the same family were examined with visual function tests, and 10 underwent bone mineral density (BMD) measurement. RESULTS: The ability of the mutated CRX protein to transactivate rhodopsin promoter was decreased by approximately 25%, and its ability to react synergistically with neural retinal leucine zipper (NRL) was reduced by more than 30%. The affected members of the family had an autosomal dominant ocular condition most closely resembling Leber congenital amaurosis (LCA) with severe visual impairment at an early age. Depending on age, affected members showed varying degrees of significant visual acuity loss, elevated dark-adaptation thresholds, significantly reduced cone and rod electroretinogram (ERG) amplitudes, and progressive constriction of the visual fields, in most cases leading to complete blindness. Six affected members had reduced levels of BMD in the spine and the hip (osteopenia). Four affected female members who were receiving long-term hormonal replacement therapy (HRT) demonstrated normal values of BMD. CONCLUSIONS: This large deletion of the CRX gene is associated with a severe form of autosomal dominant retinal degeneration. Affected members not receiving HRT showed reduced BMD (osteopenia). This phenotype may reflect the abnormal influence of mutant CRX on both retinal and pineal development.

Visual phenotype in patients with Arg41Gln and ala196+1bp mutations in the CRX gene.

Our aim was to describe the visual function characteristics of affected members from two unrelated families with different dominant mutations in the CRX gene. Standard full-field ERGs and high-intensity a-wave series were obtained. In addition, in most subjects, dark-adapted (DA) thresholds, color vision function (arrangement tests), and static perimetry were assessed. A point mutation in codon 41 of the CRX gene (Arg41Gln) was identified in family members from the RFS087 family who were tested on several occasions since 1983. Depending on age, affected members showed varying degrees of acuity loss, normal or slightly elevated DA thresholds, reduced cone a- and b-wave amplitudes, normal or minimally delayed cone b-wave implicit times, and normal rod and cone phototransduction gain parameters. An insertion mutation (Ala196+1bp) was found in two members of another family (RFS014). Affected members showed reduced visual acuity, normal or slightly elevated DA thresholds, relatively preserved rod ERG and substantially reduced or undetectable cone ERG, and normal rod phototransduction gain parameters. The Arg41Gln was associated with a late-onset, slowly progressing mild form of cone-rod dystrophy with cone loss but preserved rod and cone sensitivity until later in life. The Ala196+1bp mutation was associated with an early-onset, severe form of cone-rod dystrophy similar to that described in the original CORD2 family (Evans et al., Arch Ophthalmol 1995;113:195-201).

The electroretinogram in diabetic retinopathy.

Electroretinography (ERG) is an objective method of evaluating retinal function. Since its introduction to clinical practice in the 1940s, it has become a useful and routine diagnostic clinical tool in ophthalmology. This review summarizes the role of ERG as a clinical technique for evaluating the progression of diabetic retinopathy and as a research tool for increasing our understanding of the pathophysiology of diabetic retinopathy. Most studies show unequivocally that the different types of ERG tests detect local abnormalities or widespread pathology, even in very early stages of the disease. It seems plausible that measurements from ERG recordings, particularly the oscillatory potentials, may be useful for predicting progression from nonproliferative to the more sight-threatening stages--preproliferative or proliferative--of diabetic retinopathy. Some recent work implies that the ERG can also be a useful diagnostic method for discriminating between eyes with diabetic retinopathy and those without the condition.

Insights into the function of Rim protein in photoreceptors and etiology of Stargardt's disease from the phenotype in abcr knockout mice.

Rim protein (RmP) is an ABC transporter of unknown function in rod outer segment discs. The human gene for RmP (ABCR) is affected in several recessive retinal degenerations. Here, we characterize the ocular phenotype in abcr knockout mice. Mice lacking RmP show delayed dark adaptation, increased all-trans-retinaldehyde (all-trans-RAL) following light exposure, elevated phosphatidylethanolamine (PE) in outer segments, accumulation of the protonated Schiff base complex of all-trans-RAL and PE (N-retinylidene-PE), and striking deposition of a major lipofuscin fluorophore (A2-E) in retinal pigment epithelium (RPE). These data suggest that RmP functions as an outwardly directed flippase for N-retinylidene-PE. Delayed dark adaptation is likely due to accumulation in discs of the noncovalent complex between opsin and all-trans-RAL. Finally, ABCR-mediated retinal degeneration may result from "poisoning" of the RPE due to A2-E accumulation, with secondary photoreceptor degeneration due to loss of the RPE support role.

S-cone ERGs elicited by a simple technique in normals and in tritanopes.

PURPOSE: To measure changes in the relative spectral sensitivities of the dark adapted and light adapted ERG and thus to establish the possible contribution of rods to the 'blue cone' ERG elicited by flashes of blue light. BACKGROUND: Short wavelength stimuli in the light-adapted eye evoke small rounded b-waves which have been considered to be S-cone responses. We have recorded such responses from tritanopes, which called the assumptions into question. METHODS: Small ERGs were recorded to blue and green flashes. The stimulus was a Ganzfeld which employed light emitting diodes. ERGs were obtained in both the dark-adapted eye and after light adaptation to intense orange light (peak wavelength 610 nm). The change in sensitivity with light adaptation and the relative spectral sensitivity was determined from the voltage/log light intensity functions, using a 10 microV criterion. RESULTS: (1) peak times and changes in sensitivity did not help distinguish light-adapted rod from possible S-cone responses; (2) analysis of the change in the ratio of blue:green sensitivity from darkness to 4.4 log Td. 610 nm background suggests that in seven normal subjects, 90% or more of the ERG evoked by 440 nm flashes is generated by S-cones; (3) three tritanopes have insignificantly reduced S-cone responses. CONCLUSIONS: (1) clinical techniques used to isolate S-cone ERGs are appropriate; (2) there are at least two types of tritanope and in those we investigated, functional S-cones are probably displaced into the retinal periphery.

Spectral sensitivity of the visual system as revealed by evoked potentials in normal and anomalous trichomats.

The spectral sensitivity of the visual system upon adaptation by white light at intensity of 10,500 td was studied in Maxwellian view. The monochromatic stimuli had a size of 8 degrees and duration of 700 ms. They were superimposed on an adaptation field of 14 degrees. The spectral sensitivity was determined by the off-VEP amplitude measured from the negative peak with a latency of 75-80 ms to the positive peak with a latency of 100-110 ms. The EEG was led off monopolarly from the occipital scalp area. Eight normal trichomats, 2 protanomalous and 2 deuteranomalous subjects were investigated. Some specificity of the spectral sensitivity curve, determined by the VEP amplitude, were studied. Special attention was placed on the sensitivity decrease between lambda = 550 nm and lambda = 590 nm, which was much pronounced in the normal trichomats. Maximum sensitivity was observed at lambda = 527 nm. The sensitivity at lambda = 578 nm was lower than the maximum one by 0.8 logarithmic units or more. It is assumed that this sensitivity decrease is a manifestation of opponency between the middle wavelength and long wavelength mechanisms. In the anomalous trichomats the sensitivity decrease between lambda = 550 nm and lambda = 590 nm was much less pronounced. Maximum sensitivity was obtained at lambda = 551 nm. In the long wavelength range of the spectrum the deuteranomalous subjects showed a higher sensitivity as compared to the protanomalous ones. The obtained results suggest disturbances of color opponency in the anomalous trichomats.

Picrotoxin effects on the frog electroretinogram under different background illumination.

The effect of blockade of the GABA-ergic synapses in the frog retina by picrotoxin (PT) on ERG was studied under two conditions of background illumination (Ib): scotopic Ib with illumination level below 0.01 lx and mesopic Ib with illumination level of 2 lx. Under scotopic Ib PT produced a greater relative increase in the d-wave amplitude as compared to the b-wave. The substitution of scotopic Ib by mesopic one in untreated retinas produced a greater decrease in the b-wave amplitude than in the d-wave amplitude. The presentation of the mesopic Ib in PT treated retinas potentiated to nearly the same extent the PT effect on both b- and d-wave. So the initial shift between the amplitudes of the b- and d-wave produced by the mesopic Ib was not significantly altered by PT. The results obtained show that the GABA-ergic neurons in the mixed frog retina participate in the gain control of the ON and OFF channels in a wider range of background illumination. Their relative significance in this control seems to be greater under mesopic Ib than under scotopic Ib. We suggest that the effect of mesopic Ib on the sensitivity of the ERG b- and d-wave is complex and involves some other mechanisms in addition to the GABA-ergic one.