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PubMed1997

The effect of raised inspired carbon dioxide on normal retinal vascular development in the neonatal rat.

PURPOSE: Raised arterial carbon dioxide levels have been suggested as a risk factor for retinopathy of prematurity (ROP). We investigated the effect of raised inspired CO2 on normal postnatal vasculogenesis in the neonatal rat retina. METHODS: One hundred fifty newborn rat pups were divided among 15 mothers (n = 10 for each litter). Five litters were exposed to low CO2 (0.2%), 5 litters exposed to 6%, and 5 litters to 10% CO2. On day 7 of life the rats were sacrificed and the total retinal and vascularized retinal areas analyzed. RESULTS: The vascularized retinal area and ratio of vascularized to total retinal area were reduced in rats exposed to 6% and 10% CO2. CONCLUSIONS: Raised inspired CO2 was associated with retardation of normal retinal vascular development and increased peripheral avascular area in neonatal rats. Raised CO2 may be a risk factor for the development of abnormal neovascularization such as in ROP.

Animals↗
PubMed2004

VEGF isoforms and their expression after a single episode of hypoxia or repeated fluctuations between hyperoxia and hypoxia: relevance to clinical ROP.

PURPOSE: Fluctuations in oxygen are associated with the development of severe retinopathy of prematurity (ROP) in humans. However, the causal relationships between oxygen variability and severe ROP remain unknown. We investigated whether isoforms of vascular endothelial growth factor (VEGF) were differentially stimulated by hypoxia and by repeated fluctuations between hypoxia and hyperoxia, and whether isoforms were differentially expressed in association with intravitreous neovascularization. We also determined whether pigment epithelium-derived factor (PEDF) was dysregulated by oxygen fluctuations perhaps contributing to a delay in normal retinal vascular development. METHODS: We used the 50/10 oxygen-induced retinopathy (50/10 OIR) model that exposes newborn rat pups to repeated cycles of 24 h of 50% oxygen alternating with 24 h of 10% oxygen to cause a condition similar to human ROP. Animals were euthanized at postnatal day 2 (P2; after one cycle of 50/10% oxygen), P7 (after 3.5 cycles of 50/10% oxygen), and P14 (after seven cycles of 50/10% oxygen). Room air raised control rat pups were also exposed to a single episode of 24 h of hypoxia at P7 and P14 and assayed immediately afterwards. Retinal VEGF isoforms and PEDF were measured by RT-PCR. Total VEGF protein was measured by ELISA. RESULTS: We found that repeated cycles of hyperoxia and hypoxia caused greater expression of VEGF protein compared to control than did a single cycle of hyperoxia and hypoxia. VEGF164 mRNA had a greater fold change over control after repeated oxygen fluctuations than after a single episode of hypoxia. However, the other isoforms, VEGF188 and VEGF120, were expressed to a similar degree regardless of whether the stimulus was a single episode of hypoxia or repeated fluctuations in oxygen. VEGF164 was the predominant isoform expressed at the time of maximal intravitreous neovascularization. Retinal PEDF expression was elevated in pups in the 50/10 OIR model compared to control at P7, immediately after 50% oxygen. PEDF expression in the experimental group was similar to control at P18, when intravitreous neovascularization occurred. CONCLUSIONS: Repeated fluctuations in oxygen results in a greater expression of the pathologic isoform, VEGF164, than does hypoxia alone. However, the other isoforms were upregulated to an equivalent degree over control by repeated fluctuations in oxygen or a single episode of hypoxia. Total VEGF protein was increased to a greater degree by repeated fluctuations in oxygen compared to a single cycle of oxygen. PEDF was increased over control early in the 50/10 OIR model and may play a role in the observed delay in retinal vascularization. These findings provide insight into the effect of repeated oxygen fluctuations on the development of severe ROP in preterm infants.

Animals↗
PubMed1977

Retinal enzyme activities under hypoxic conditions prior to neovascularization.

In an effort to demonstrate biochemical changes occuring in malperfused retinas, oxygen-induced retrolental fibroplasia was produced in kittens. Immediately before the onset of vasoproliferations, that is in the stage of maximal hypoxia, the activities of lactate dehydrogenase (LDH), glucose-6-phosphate dehydrogenase (G-6-PDH), malate dehydrogenase (MDH) and isocitrate dehydrogenase (ICDH) were determined. The activity of MDH was found to be significantly decreased, whereas the activities of the other enzymes showed no major changes.

Animals↗
PubMed2006

Retinal function following transpupillary thermotherapy for occult choroidal neovascularization in age-related macular degeneration: a short-term study by focal electroretinography.

PURPOSE: To assess short-term changes in macular function after transpupillary thermotherapy (TTT) in patients with occult subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD), using focal electroretinography (FERG). METHODS: Twenty-five patients with occult subfoveal CNV due to AMD were treated with TTT delivered using an infrared (810 nm) diode laser (spot size 3.0 mm, laser power 400-600 mW, duration 60 seconds). All patients were clinically evaluated before, 1 and 6 weeks after treatment. Snellen visual acuity (VA) was measured at each visit. Fluorescein angiography (FA) was performed at baseline and 6 weeks after TTT. Focal ERGs were recorded in all patients immediately before and 1 week after TTT in response to an 18-degree diameter, 41 Hz flickering spot (630 nm) centred on the fovea, presented on a steady background in Maxwellian view. A subgroup of 12 patients was also re-tested by FERG at 6-weeks post-TTT. RESULTS: No significant changes in mean FERG amplitude and phase were observed across the different recording sessions before and after TTT. One week after TTT, four patients had significant (> 2 SD from baseline variability) increases in FERG amplitude and/or phase advances, one had a decrease in amplitude and four had phase delays, compared to baseline. The remaining 15 patients had stable FERGs. Six weeks after TTT, four patients had significant increases in FERG amplitude and/or phase advances, four had decreases in amplitude and/or phase delays, and four had stable FERGs, compared to baseline. Improvement in FERG parameters after TTT was always associated with an improvement in VA and a decrease in exudation. Patients with post-TTT FERG deterioration had stable or deteriorated clinical pictures. At either 1 or 6 weeks post-TTT, the FERG amplitude increase was inversely correlated (p < 0.05) with the baseline FERG amplitude and VA. CONCLUSIONS: Three major conclusions can be drawn: in a short-term follow-up, TTT was not found to be associated with significant changes in macular function; FERG improvement was associated with VA improvement, and the increase in FERG amplitude was greatest in patients with the worst baseline acuity.

Aged↗
PubMed1999

Indocyanine green angiography and retinal sensitivity after photodynamic therapy of subfoveal choroidal neovascularization.

Photodynamic therapy (PDT) is currently being evaluated in clinical trials for the treatment of choroidal neovascularization (CNV). Preliminary results indicate that PDT achieves immediate absence of leakage from CNV while maintaining visual acuity. Indocyanine green angiography reveals a reduction in CNV size and a persistent decrease in leakage activity after PDT. PDT appears to be characteristically accompanied by choroidal perfusion changes that regularly resolve within 3 months. Microperimetry shows an improvement of the central visual field with a decrease in scotoma size and intensity. Repeated PDT applications do not cause additional damage to the treated area, but might further enhance the recovery of macular function. A placebo-controlled, multi-center trial (TAP trial) evaluating the benefit of repeated PDT treatments in 3-month intervals is currently underway.

Choroidal Neovascularization↗
PubMed1996

Inhibition of preretinal and optic nerve head neovascularization in pigs by intravitreal triamcinolone acetonide.

PURPOSE: The authors tested the antiangiogenic properties of intravitreally administered triamcionolone acetonide in a pig model of preretinal neovascularization to determine the effectiveness of this therapy in preventing neovascularization. METHODS: In 14 eyes of seven pigs, branch retinal vein occlusions were created in a standardized manner using photodynamic thrombosis with rose bengal dye and thermal burns from the argon green laser. Intravitreal injection of approximately 4 mg of triamcinolone acetonide was performed in one eye of each animal, and eyes were followed clinically for 12 weeks with ophthalmoscopy and fundus photography. A standardized grading system was developed to permit masked assessment of disc proliferations from fundus stereophotographs. After death, all neovascularization was confirmed histopathologically and a final grade was assigned to each eye. Statistical analysis employed use of a nonparametric test of the paired data. RESULTS: Significant inhibition of neovascularization was observed in triamcinolone-treated eyes (P = 0.0156). Although none of the steroid-injected eyes demonstrated clinically evident new vessels, histopathologic and photographic analysis results demonstrated fine new vessels on the optic disc in four eyes. In all of the untreated eyes, neovascularization of a moderate (II) to high (III to IV) grade developed. CONCLUSIONS: Intravitreal triamcinolone acetonide effectively inhibited preretinal and optic nerve head neovascularization in the pig model. The grading system used permitted masked assessment of outcome and paired analysis allowed a conclusion to be drawn from a relatively small number of eyes. The mechanisms by which triamcinolone acetonide inhibits neovascularization remain to be elucidated.

Animals↗
PubMed2026

The role of adjunctive aqueous suppressants for anti-vascular endothelial growth factor therapy: A systematic review.

Our goal is to determine whether adjunctive aqueous suppressants (topical &#x3b2;-blockers, carbonic anhydrase inhibitors, or oral acetazolamide) enhance outcomes of anti-vascular endothelial growth factor (anti-VEGF) therapy for diabetic macular edema (DME), retinal vein occlusion (RVO), and neovascular age-related macular degeneration (nAMD), focusing on retinal thickness, visual acuity, injection burden, intraocular pressure (IOP), and safety. DME, RVO, and nAMD are leading causes of vision loss treated with repeated intravitreal injections, yet many eyes show persistent fluid. Aqueous suppressants are inexpensive and widely available, with potential to prolong intravitreal drug residence and improve outcomes, but their clinical value remains uncertain. Following a registered protocol, we searched 4 databases (January, 2000 toMay, 2025) for randomized and comparative studies evaluating adjunct aqueous suppressants with anti-VEGF therapy. Primary outcome was change in retinal thickness; secondary outcomes included visual acuity, injection burden, IOP, and adverse events. Risk of bias was assessed and findings synthesized narratively. Twelve studies (7 randomized trials; 495 eyes) met inclusion criteria. In DME, 3 of 4 trials showed greater thickness reduction with adjunctive dorzolamide (&#xb1;timolol), although visual gains were inconsistent. In RVO, 1 trial suggested transient anatomical benefit, whereas oral acetazolamide showed no added effect. In nAMD, adjunctive dorzolamide-timolol reduced residual fluid in refractory cases without visual or treatment-sparing benefit. Topical therapy produced modest IOP reductions without serious adverse events. Adjunct aqueous suppressants may provide limited short-term anatomical benefit, particularly in DME and refractory nAMD, but consistent functional or durability effects are not found in this study. Larger, longer-term randomized studies are needed.

Humans↗
PubMedDate not supplied

Evolution of retinal pigment epithelium detachment after photodynamic therapy for choroidal neovascularization in age-related macular degeneration.

PURPOSE: To report a case of pigment epithelium detachment (PED) which appeared after photodynamic therapy (PDT) and was followed up for 50 months. METHODS: Case report. RESULTS: A 71-year-old woman with occult choroidal neovascular membrane due to age-related macular degeneration (ARMD) developed PED 48 hours after PDT. The patient was studied with fluorescein angiography (FA) and optical coherence tomography (OCT). Fluorescein angiographic evidence of PED remained essentially unchanged during the follow-up period of 50 months. Although OCT initially gave clear evidence of PED, in the last 12 months of follow-up the PED appears to have resolved. CONCLUSIONS: Photodynamic treatment could be involved in the occurrence of PED in occult choroidal neovascular membrane due to ARMD. In this particular case OCT could be considered since it offers useful information in the pretreatment and the post-treatment follow-up period.

Aged↗
PubMed1989

Retinal blood flow regulation and the clinical response to panretinal photocoagulation in proliferative diabetic retinopathy.

Bidirectional laser Doppler velocimetry and monochromatic fundus photography were used to investigate retinal hemodynamics before and after panretinal photocoagulation (PRP) in 25 eyes of 23 diabetic patients with proliferative retinopathy. After PRP, there was a significant decrease in retinal volumetric blood flow rate and an increase in the retinal vascular regulatory response to hyperoxia (R). A significant association was found between the presence or absence of regression of neovascularization and the increase or decrease in R after PRP. Eyes that showed regression of neovascularization had significantly larger average R after PRP than eyes that did not show regression. Lack of improvement in R after PRP may be related to the presence of remaining ischemia or hypoxia in eyes that continue to show proliferation after PRP.

Adult↗
PubMed1989

Extracellular matrix alterations precede vascularization of the retinal pigment epithelium in dystrophic rats.

In Royal College of Surgeons (RCS) rats, the defective retinal pigment epithelium (RPE) fails to phagocytose the shed outer segment membranes, and the photoreceptors degenerate. Following degeneration of the photoreceptors, neovascularization and vitreo-retinal membranes (VRMs) develop. Blood-retinal barrier abnormalities at the level of the RPE suggested that Bruch's membrane extracellular matrix filtration barriers might also be abnormal. To study the progression of RPE cell, extracellular matrix and vascular alterations in the dystrophic retina, we used the cationic tracer polyethyleneimine and electron microscope morphometric techniques. At two weeks in the RCS retina, the RPE and retinal vessels, and their basal laminae, appeared normal. By two months, the RPE was hypertrophic and duplicated in some areas, and flattened in others. The RPE basal lamina was thickened (171% of the control, p less than .01), and there were more anionic sites along the RPE basal surface (158% of the control, p less than .01). Patches of displaced basal lamina material appeared within the RPE basal infoldings. By four months and later numerous retinal vessels were present within the RPE layer. In addition, cords of migrating RPE cells surrounded presumptive new vessels branching from the RPE layer towards the inner limiting membrane. The RPE-associated vessels exhibited diaphragmed fenestrae and channels, unlike normal retinal vessels, and their basal laminae were marked by anionic sites. These observations of RPE and extracellular matrix changes prior to vascular proliferation, and VRM formation in the dystrophic retina suggest that the RPE-associated extracellular matrix changes may contribute to vascular alterations in the dystrophic retina. A preliminary report of these findings has been presented previously.

Aging↗
PubMed1981

[Retinal findings in thalassemia (author's transl)].

Two patients had neovascularizations, bleeding and enclosed vessels or pigmented foci on the retina. The analysis of the hemoglobin showed a raised HbA2 fraction, indicating that they could be considered heterozygous gene carriers of beta-thalassemia. An electrophoretic-spectrophotometric method of determining the hematologic changes is described by means of which thalassemia minima can be diagnosed reliably.

Diagnosis, Differential↗
PubMed1992

[Retinal vein occlusion. II. Clinical picture and photocoagulation therapy].

The author analyze in detail the clinical findings in occlusion of a branch or trunk of the retinal vein. Occlusion of a branch of the retinal vein has on the whole a favourable prognosis and the resulting vision is in about 60% 6/12 better. This depends in particular on three factors: site of occlusion, calibre of the occluded vein and grade of venous obstruction. In the remaining 40% of patients with occlusion of a branch the resulting vision is 6/18 or poorer and in half of the latter patients it is poorer than 6/60. The most frequent cause of unsatisfactory resulting vision in occlusion of a branch of the retinal vein are chronic macular oedema and neovascularization. In occlusion of the trunk of the retinal vein there is the danger that the residual vision will be lost in conjunction with the possible development of a neovascular glaucoma. The possibilities of a favourable therapeutic effect by using an argon laser are much greater in occlusion of a branch than in occlusion of the trunk of the retinal vein, where the author concentrates attention on prevention of a neovascular glaucoma.

Humans↗
PubMed2005

Macular thickness in patients with choroidal neovascularization determined by RTA and OCT3: comparative results.

AIMS: The authors conducted a study to compare retinal thickness in patients with choroidal neovascularization (CNV) using optical coherence tomography (OCT) and retinal thickness analyser (RTA). METHODS: In all, 11 eyes from 11 patients with subfoveal choroidal neovascularization were examined with OCT and RTA. RESULTS: Three patients could not be explored by RTA due to lack of fixation and high myopia. The mean foveal thickness was 289.9+/-92.1 microm with OCT and 207.7+/-60.8 microm with RTA. The mean perifoveal thickness was 293.8+/-46.3 microm and 200.8+/-61.3 microm, respectively. The maximal perifoveal thickness measured by OCT was 335+/-104.0 microm and 316+/-86.8 microm by RTA. CONCLUSION: OCT and RTA are able to detect increases in retinal thickness due to the presence of CNV and of fluid extravasation. They can be used in measuring retinal thickness in patients with CNV, although measures are not comparable between both systems.

Aged↗
PubMed1997

Laser treatment in subjects with high-risk clinical features of age-related macular degeneration. Posterior pole appearance and retinal function.

OBJECTIVES: To verify that a few laser lesions in the posterior pole can cause drusen to resolve in patients with age-related macular degeneration, and to document central retinal sensitivity as drusen resolve. DESIGN: In a pilot study, 12 patients considered to be at high risk for sight-threatening complications from age-related macular degeneration were treated with 12 argon laser lesions in the posterior pole, with review for 12 to 24 months. RESULTS: Choroidal neovascularization developed in 1 patient 8 months after treatment, with consequent loss of central vision. In 9 of the remaining 11 patients, high-risk characteristics of drusen were reduced. Four patients had retinal pigment epithelial depigmentation, and all maintained 20/40 visual acuity at 12 months. One patient lost 3 lines of vision due to geographic atrophy after 12 months. Scotopic retinal threshold was elevated before treatment in 8 patients, compared with an age-matched comparison group. Of these, 4 patients underwent retesting 3 to 6 months after treatment, and all had improved thresholds, but only 1 patient sustained the improvement at 12 months. At 12 months, 3 of the 8 patients showed an improvement in their mean retinal threshold. Of those in whom the mean retinal threshold worsened, the mean elevation in threshold was not more than 0.6 log units. CONCLUSIONS: A few laser lesions in the posterior pole leads to resolution of drusen. There does not appear to be an increased risk for choroidal neovascularization. Retinal threshold measurements show no indication of geographic atrophy at 1 year, but cannot be excluded as a late outcome. Laser treatment may reduce the risk for profound sight-threatening lesions in age-related macular degeneration.

Aged↗

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