Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity.

Retinopathy of prematurity (ROP) is initiated by hyperoxia-induced obliteration of newly formed blood vessels in the retina of the premature newborn. We propose that vessel regression is a consequence of hyperoxia-induced withdrawal of a critical vascular survival factor. We show that regression of retinal capillaries in neonatal rats exposed to high oxygen, is preceded by a shut-off of vascular endothelial growth factor (VEGF) production by nearby neuroglial cells. Vessel regression occurs via selective apoptosis of endothelial cells. Intraocular injection of VEGF at the onset of experimental hyperoxia prevents apoptotic death of endothelial cells and rescues the retinal vasculature. These findings provide evidence for a specific angiogenic factor acting as a vascular survival factor in vivo. The system also provides a paradigm for vascular remodelling as an adaptive response to an increase in oxygen tension and suggests a novel approach to prevention of ROP.

Microsurgery of the retina with a needle-guided 193-nm excimer laser.

This article presents a method used to guide the beam from an argon fluoride excimer laser to make it suitable for microsurgical purposes and confine it to areas that can be varied in dimension from 1 micron to tens or hundreds of microns. This approach guides the excimer laser beam with an articulated mechanical arm and confines it with variable-diameter tapered tubes, possibly allowing the use of this laser in in vitro retinal surgery with endolaser techniques. Currently, because of the lack of a delivery and focusing system for the 193-nm argon fluoride beam and its absorption by biologic liquids, this laser is used exclusively in ophthalmology for topical applications, such as corneal sculpting. This new method resolves these problems in a unique way with impressive results. Specifically, it was shown that, with this needle-guided excimer laser, it is possible to remove retinal tissue accurately without detectable damage to surrounding cells. Applications of this new technique in retinal surgery are discussed.

Vitreoretinal surgery assisted by the 193-nm excimer laser.

PURPOSE: Ablating and cutting vitreoretinal membranes using a 193-nm excimer laser-based microsurgical system. METHODS: A 193-nm microsurgical system enables delivery of the beam into a fluid medium to cut preretinal and subretinal membranes. Two patients with proliferative diabetic retinopathy and one patient with proliferative vitreoretinopathy were treated with this new device. RESULTS: Gentle ablation and cutting of the preretinal and subretinal membranes without exerting any traction on or apparent damage to the neighboring tissue was achieved. CONCLUSIONS: The technology is applicable to a variety of intraocular vitreoretinal surgical procedures.

Vitreoretinal ablation with the 193-nm excimer laser in fluid media.

PURPOSE: To ablate retina and vitreous membranes using the 193-nm argon fluoride excimer laser in a fluid medium. METHODS: A special delivery system for the 193-nm excimer laser was developed that enabled the delivery of the laser into high-absorption liquid environments. The system was tested on the retina in an in vitro cup preparation of cow's eyes, and also in vivo on retina and vitreous membranes of rabbit eyes. The depth of cut as a function of laser energy was determined for an ablating needle with a 0.25-mm exit diameter. RESULTS: Gentle cutting of retinal tissue and of vitreous membranes was obtained in an energy range of 0.075 to 0.25 mJ/pulse. At the energy level of 0.075 mJ/pulse, four pulses were required for full-depth cut formation in rabbit retina, whereas at energy levels greater than 0.17 mJ/pulse, one pulse was sufficient for full-depth cut formation. The maximal rate of cutting achieved for the bovine retina was 2 mm/sec at a 20-Hz repetition rate of the laser. Ablation occurred only when the tip was held in contact with the tissue. CONCLUSIONS: The technology described herein appears to be advantageous and applicable to a variety of vitreoretinal surgical procedures.

In vivo angiogenic activity of interleukins.

Interleukin 1 incorporated into Elvax-40 (ethylene-vinyl-acetate copolymer consisting of 40% vinyl-acetate by weight) induces a rapid and strong angiogenic stimulus when implanted in rabbit corneas at a distance of 2.5 mm from the limbus. A constant and reproducible neovascular stimulus was observed with 5 ng per implant of recombinant human interleukin 1 alpha or 100 ng per implant of recombinant human interleukin 1 beta. At these concentrations, neither tumor necrosis factor nor interleukin 2 induced any neovascular stimulus. These data are interpreted as an indication for the possible role of interleukin 1 in angiogenesis of ocular (and other) tissues. As interleukin 1 is produced by various cells, it is hypothesized that this molecule may be the "unitarian angiogenic factor."

Effect of eye patching on ocular surface.

We studied the effect of pressure patching in 27 medical students. Fourteen students had pressure patching in one eye (group 1) and 13 (group 2) had light patching. The fellow eye of each volunteer remained unpatched (group 3). Clinical signs and symptoms were scored and evaluated at the first and the following (after overnight) examinations. Before patching no subject had any of the clinical signs or symptoms. After the patch was removed in groups 1 and 2, all except one volunteer in each group had clinical signs or symptoms, or both, whereas in group 3, none had clinical signs or symptoms. Group 1 had greater scores for clinical signs (P = .019) and for symptoms (P = .038) as compared to group 2. In group 1, two participants did not complete the study period (by removal of the patch) because of severe discomfort and three had temporary irregularities in corneal surface with temporary decrease of vision. We suggest that pressure patching may cause discomfort and changes in visual acuity that are usually attributed to other reasons.

Efficacy of doxycycline and tetracycline in ocular rosacea.

We compared the effects of doxycycline and tetracycline hydrochloride on the subjective symptoms in ocular rosacea. Twenty-four patients with symptomatic ocular rosacea were randomly assigned to two groups and treated with doxycycline 100 mg/day (group 1, 16 patients) or tetracycline hydrochloride 1 g/day (group 2, eight patients). The dosages of each drug were gradually tapered and discontinued according to symptomatic response. At each examination all the manifesting symptoms were scored by the patients. Patients were followed up from six weeks to three years. After six weeks of drug treatment, all patients except one had symptomatic improvement. Although most of the scores of the symptoms were significantly decreased in both groups, greater symptomatic relief occurred in the tetracycline hydrochloride-treated patients (P = .041). However, after three months of treatment there was no significant difference in symptoms between the two groups. Gastrointestinal tract complications occurred in two of the 16 patients (12.5%) in group 1 and in three of the eight patients (37.5%) in group 2. Both tetracycline hydrochloride and doxycycline can control the symptoms of ocular rosacea.

Upregulated expression of vascular endothelial growth factor in proliferative diabetic retinopathy.

AIMS/BACKGROUND: Vascular endothelial growth factor (VEGF) is a hypoxia induced angiogenic factor. Recent studies have shown that high levels of VEGF accumulate in the vitreous of patients with proliferative diabetic retinopathy (PDR). The purpose of the present study was to identify the retinal cells that upregulate VEGF expression in human PDR patients representing progressive stages of retina deterioration. METHODS: Thirteen formalin fixed and paraffin embedded enucleated eyes with PDR were used (eyes were enucleated because of being blind and painful as a result of neovascular glaucoma). Thin retina sections were hybridised in situ with a VEGF specific probe, to identify cells producing VEGF mRNA. RESULTS: All eyes with PDR showed upregulated expression of VEGF mRNA, specifically in the cells of the neurosensory retina. VEGF expression was upregulated in all three nuclear layers--namely, the ganglion cell layer, the inner nuclear layer, and the outer nuclear layer. However, in each patient, VEGF producing cells were mostly distributed in a different layer, or even confined to a specific region in that layer. For example, expression by the outer nuclear layer was mostly detected in detached (presumably hypoxic) regions of the retina. CONCLUSIONS: Progression of PDR is distinguished by a sustained, upregulated expression of VEGF by the neurosensory retina. Cells in all retina layers can potentially contribute to augmented VEGF production. The restricted population of VEGF producing cells in each case is likely to represent cells residing in ischaemic regions of the retina. Thus, VEGF may function as a linking factor between retinal ischaemia and PDR associated neovascularisation.

Uveal lymphoid infiltrates: immunohistochemical evidence for a lymphoid neoplasia.

A 67-year-old man presented with a diffuse choroidal and ciliary body infiltrate, suggesting clinically and ultrasonographically a diffuse uveal melanoma. After enucleation both morphological and immunohistochemical data were highly suggestive of a diffuse, low-grade B cell lymphoma or lymphoplasmacytic immunocytoma. The difficulties of clinical and histopathological differential diagnosis of uveal lymphoid infiltrates are emphasised. In view of the excellent life prognosis of these tumours, treatment of the patient should be directed towards the preservation of ocular function.

Intraocular lens implantation in an underdeveloped country.

The results of 152 intraocular lens implantations performed at Mbabane Government Hospital, Swaziland, Africa, on 114 African patients with senile cataracts are presented. Surgery was performed with manual equipment and procedures. Lens implantation was accompanied by a low rate of postoperative complications. Uncorrected visual acuity of 20/120 or better was achieved in 79.6% of patients. The advantage of IOL implants over low-cost aphakic spectacles in Third World countries is discussed.

Promoting effect of n-decylmethyl sulfoxide on the penetrability of the optic nerve for lidocaine HCl in cats.

We examined the effect of n-decylmethyl sulfoxide (n-decylMSO) on the resistance of the optic nerve sheath to the penetration of lidocaine hydrochloride. Three series of experiments were carried out in living cats, administering lidocaine with and without n-decylMSO. The visual evoked potential (VEP) and optic nerve response (ONR) were measured. The results obtained indicated that n-decylMSO increased the penetration of lidocaine. The presence of lidocaine (1%) and n-decylMSO (2.5%) decreased the ONR amplitude from 120 to 15 microV after a time lag of 105 min, and VEP decreased from 9.0 to 5.5 microV. This effect was preserved during the experiment. Histological examination showed only minimal changes in the optic nerve and the eye globe and its contents. Some infiltration of mononuclear cells was found around the optic nerve sheath.

Single dosage of mitomycin C for prevention of recurrent pterygium: preliminary report.

We studied the recurrence rate of pterygium after administration of a single dosage of topical mitomycin C at the completion of pterygium surgery. Forty patients who had advanced or recurrent pterygium underwent excision of pterygium, leaving the sclera bare. Patients were randomized in a masked fashion into two groups of 20 patients each. Group 1 received a single dosage of topical 0.02% mitomycin C for 5 min at the completion of the surgery whereas group 2 underwent the same procedure but received NaCl 0.9% instead of mitomycin C. Patients were followed from 6 to 15 months in a masked manner. The pterygium recurred in one patients (5%) in group 1, whereas in group 2 the recurrence rate was 45% (p = 0.0035). Formation of dellen and a delay of epithelialization for 5 weeks were found in one patient in group 2. No complications were observed in patients in group 1. This study indicates the possible advantage of administration of a single dosage of 0.02% mitomycin C for postoperative prevention of recurrence of pterygium.

Threshold scaling limits of RO concentrates flowing in a long waste disposal pipeline.

Disposal of RO concentrates emanating from inland brackish water desalination plants presents a difficult environmental problem. The solution adopted by Mekorot--the National Water Company of Israel--is to construct a 30 km waste disposal pipeline for collecting concentrates emanating from several RO desalination plants and discharging them into the sea. The discharged concentrates are highly supersaturated with respect to CaCO3. Scale precipitation during concentrate flow through the RO module is inhibited by the presence of anti-scalants. The retention time of the concentrate solution in the discharge pipe will exceed 100 hours. This raises the issue of the risk of scale precipitation in the discharge pipe that could impair its proper functioning. The aim of the present study was to provide data for guiding the design and operation of the disposal pipeline. The extent of the induction period prior to the onset of precipitation was measured in a pilot plant simulating flow of concentrate solutions dosed with anti-scalants. The parameters investigated were the scaling potential, the anti-scalant concentration and the presence of a mixture of several anti-scalants. The results of this study provide threshold scaling limits under various conditions.

Fellow eye effect of unilateral intravitreal bevacizumab injection in eyes with diabetic macular edema.

AIMS: Anti-vascular endothelial growth factor compounds are routinely used for the treatment of diabetic macular edema (DME). We aim to evaluate for the existence and magnitude of treatment effect on fellow un-injected eyes. METHODS: A consecutive group of patients with bilateral DME who received unilateral bevacizumab injections was retrospectively evaluated. Data collected included demographics, ophthalmic and systemic findings, and optical coherence tomography (OCT) measurements of macular thickness. RESULTS: Thirty-five patients were evaluated. Mean follow-up was 245 days (range: 30-800), and the mean number of bevacizumab injections was 3.6 (range: 1-11). At end of follow-up, the mean (SD) OCT central subfield thickness reduced by 72 ± 112 micron in the injected eye (from 469 ± 139 to 397 ± 120 micron; P=0.001), while in the non-injected eye it reduced by 49 ± 75 micron (from 380 ± 130 to 331 ± 106 micron; P<0.001). Sixteen injected eyes (45.7%) showed central subfield thickness reduction of ≥50 micron while 10 (28.6%) non-injected eyes showed such thickness reduction. Improved VA following treatment was detected in 14 (40%) injected eyes and in 15 (43%) non-injected eyes. CONCLUSIONS: Unilateral bevacizumab injections in patients with bilateral DME are often associated with bilateral response. SUMMARY STATEMENT: Anti-vascular endothelial growth factor compounds are routinely used for the treatment of diabetic macular edema (DME). In this retrospective study, we show that unilateral bevacizumab injections often result in reduction of the macular thickness in the fellow un-injected eye.

Intravitreal bevacizumab therapy for neovascular age-related macular degeneration associated with poor initial visual acuity.

AIM: The aim of the study was to assess the efficacy of intravitreal bevacizumab injections for eyes with neovascular age-related macular degeneration (NVAMD) and poor initial visual acuity (VA). METHODS: A retrospective study of 44 consecutive treatment-naïve eyes with NVAMD who had initial VA of 0.1 decimal or worse, and that were treated with intravitreal bevacizumab injections, was undertaken. Charts, optical coherence tomography (OCT) and fluorescein angiograms (FAs) were reviewed for the purpose of the study. RESULTS: Mean lesion size was 3375 (SD 2116) microm, all lesions showed sub- or intra-retinal fluid in OCT, and active neovascularisation comprised 41.6 (SD 17.7)% (range 10-90%) of the lesion area according to FA. The mean follow-up time was 3.9 (SD 5.8) (range 1-21) months. Patients received a mean of 2.6 (SD 2.4) bevacizumab injections (range 1-14), and mean VA improved from 1.85 (SD 0.64) to 1.52 (SD 0.77) LogMAR (p = 0.002). At final examination, nine eyes (20%) had reduced VA, ten eyes (23%) had stable VA and 25 eyes (57%) had improved VA compared with baseline. Following treatment, mean macular thickness was reduced from 332 (SD 98) to 248 (SD 79) microm (p<0.0001). CONCLUSIONS: Poor initial VA should not prevent use of bevacizumab in eyes with NVAMD. Selection of patients with signs of active neovascularisation based on ophthalmoscopy, OCT and FA may increase the likelihood of a favourable response to treatment.

Prevalence of clinical asymptomatic retinal detachment in myopic population.

AIM: To evaluate the prevalence of clinical asymptomatic retinal detachment (ARD) in myopic population. METHODS: A retrospective study including all myopic individuals who underwent ophthalmic evaluation prior to excimer laser procedures at the Hadassah Center for Refractive Surgery between March 2002 and March 2006. Medical records were reviewed to extract demographics and refraction, and to identify patients who were diagnosed as having asymptomatic retinal detachment. RESULTS: Data were collected on 6547 myopic individuals (12 815 eyes); of these, 2907 (44.4%) were males, and 3640 (55.6%) were females. The mean age was 31.5 (SD 10) years (range 18-64 years). The mean preoperative spheric equivalence was -4.42 (2.07) (range -0.75 to -16.00). The mean best spectacle-corrected visual acuity was 20/20 (range 20/32 to 20/12.5). Five eyes (0.039% or one of approximately 2563 eyes) of four patients had clinical ARD which was diagnosed during the routine preoperative examination. Three eyes underwent successful scleral buckling procedure while two patients were lost to follow-up. CONCLUSIONS: Clinical asymptomatic retinal detachment is uncommon, accounting for a minority of retinal detachments in myopes, and may be diagnosed during routine ophthalmoscopy prior to a refractive procedure.

Lack of benefit of early awareness to age-related macular degeneration.

AIMS: To assess the rate of early awareness to the presence of age-related macular degeneration (AMD) and whether it enables early detection of transition to neovascular AMD (NVAMD) as compared with patients whose first presentation to an ophthalmologist is already at the neovascular stage of disease. METHODS: A retrospective analysis of 268 eyes of 268 consecutive patients with newly diagnosed NVAMD that were treated in a tertiary referral centre was performed. Patients were classified into those who were unaware (Group 1), or aware (Group 2), of the fact that they had AMD before diagnosis of NVAMD. Visual acuity, lesion size and composition, and demographics were compared between both groups. RESULTS: In all, 185 patients (69%) and 83 patients (31%) were classified to Groups 1 and 2, respectively. Patients in Groups 1 and 2 had similar demographic characteristics, presenting visual acuity and lesion size, and lesion compositions. Group 1 patients were more likely to have a positive history for smoking (41 vs26% in Group 2, P=0.03), whereas Group 2 patients were more likely to have positive family history for AMD (20 vs10%, P=0.02). CONCLUSIONS: These data suggest that current screening methods fail to identify the majority of patients with AMD before the development of NVAMD. The findings also demonstrate that in the routine clinical setting, prior awareness of AMD may not facilitate early detection of treatable choroidal neovascularization lesions.

Paediatric vs adult retinal detachment.

OBJECTIVE: To evaluate the causes, incidences, characteristics, and treatment outcomes of paediatric vs adult retinal detachment. PATIENTS AND METHODS: One hundred and sixty (136 patients) out of 2408 consecutive retinal detachments (6.6%) at our facility occurred in children under the age of 18 years. Of them, 144 eyes (90%) of 127 (93%) children were treated and compared with a sample of 56 consecutive retinal detachments in 50 adults (over the age of 18 years). The parameters for comparison included cause, type of retinal detachment, its extent, macular involvement, number of tears, number and types of surgery, and the anatomic and functional surgical outcome. RESULTS: Statistically significant differences were found in the type of retinal detachment. Rhegmatogenous RD was less common (P=0.004), and exudative RD was more common (P=0.021) in the paediatric group. Ocular trauma and ocular syndromes were more common in the paediatric group (P<0.001), while myopia, posterior vitreous detachment, and retinal detachment following cataract surgery were less common in this group compared with adults (P<0.001, <0.001, and 0.001, respectively). Ocular pathologies associated with retinal detachment were more common in the paediatric group (P<0.001). Initial and last visual acuity of >20/400, last visual acuity of >20/40, and retinal complete reattachment were higher in adults (P<0.001). CONCLUSIONS: The type of retinal detachment, causes and outcomes were statistically different between paediatric and adult cases. The less successful functional and anatomical outcomes of retinal detachment surgery in children may reflect the different aetiologies and indicate the need for aetiology-specific treatment strategies according to each aetiology.

Use of fibrin glue in ocular surgery.

Cryoprecipitate and thrombin were used to prevent bleeding and induce permanent conjunctival attachment in ten cases of retinal detachment, 40 cases of extracapsular cataract extraction, and ten cases of strabismus. This method proved to be a good alternative to suturing the conjunctiva in each of the above-mentioned surgical procedures, and appears to result in a better and more comfortable postoperative course.