A review of anti-VEGF agents for proliferative diabetic retinopathy.

Previous research has implicated vascular endothelial growth factor (VEGF) in the pathogenesis of diabetic retinopathy (DR). Although many studies reviewed the use of anti-VEGF for diabetic macular oedema, little has been written about the use of anti-VEGF for proliferative diabetic retinopathy (PDR). This study is a review of relevant publications dealing with the use of anti-VEGF for the treatment of PDR. The articles were identified through systematic searches of PUBMED and the Cochrane Central Register of Controlled Trials. At the end of each section, we summarized the level of evidence of the scientific literature. Off-label use of anti-VEGF agents was found to be beneficial in PDR, especially in cases with neovascular glaucoma, persistent vitreous haemorrhage, and before vitrectomy. The disadvantages of the use of anti-VEGF are its short-effect duration, causing tractional retinal detachment in cases with pre-existing pre-retinal fibrosis and endophthalmitis in rare cases. There is no conclusive evidence from large randomized trials regarding the efficacy of anti-VEGF treatment in PDR. However, numerous case series, sound biochemical mechanism of action, and increasing experience with using anti-VEGF drugs can be used to support the ongoing use of this treatment modality in selected patients.

Burkitt's lymphoma presenting as oculomotor palsy in an hiv-positive patient.

PURPOSE: To report a case of Burkitt's lymphoma (BL) in an HIV-positive patient presenting as complete third nerve palsy. METHODS: Interventional case report. A 34-year-old man presented with headache, left eye pain, diplopia, and complete ptosis of several hours' duration. Left eye examination disclosed complete third nerve palsy with pupillary involvement. Significant hepatomegalia was noted at physical examination and computed tomography (CT) scan of the abdomen showed multiple solid lesions. RESULTS: Liver biopsy was consistent with Burkitt's lymphoma. Bone marrow biopsy was normal. Brain imaging was normal. Work-up also revealed positivity for human immunodeficiency virus. Chemotherapy treatment was started. Two months later, ocular motility examination was normal. CONCLUSIONS: Although BL affects the central nervous system very rarely, BL should be considered in any immunosuppressed patient presenting with diplopia or ophthalmoparesis.

Broth cultures yield vs traditional approach in the workup of infectious keratitis.

PURPOSE: To elucidate whether BACTEC Peds Plus F broth, usually used for culturing body fluids in paediatric departments, can be used for corneal cultures from cases with clinically suspected infectious keratitis, and to compare yields between this method and traditional methods (blood agar, chocolate agar, a fungal media, and swab transport media). METHODS: All cases with newly diagnosed, nonviral, clinically suspected infectious keratitis with no prior antibiotic therapy, were cultured both in the BACTEC Peds Plus F broth and the traditional method. McNemar's test was used for pairwise comparisons of the rates of positive growth between the two groups. RESULTS: In total, 30 eyes were included in this study. The growth rates for the traditional method and the BACTEC broth were similar (50.0 and 53.33%, respectively, P=1.0). The overall growth rate for the two methods combined was 73.33%, which is 45.29% higher than the reported yield in the literature (average of 50.47%). CONCLUSIONS: Our results show that BACTEC Peds Plus F broth can be used successfully in the work-up of clinically suspected infectious keratitis. The method has, apparently, several advantages over the 'Traditional method:' time-savings, as only one medium needs to be inoculated, transportation to the laboratory is simpler as there is no need for immediate incubation, and there is no need to keep and maintain a supply of fresh agar media. This method is especially suitable for office settings and remote clinics, but also can be used in hospital setting, as an adjunct, when available, to increase the growth yield.

Central corneal thickness and its relationship to the patient's origin.

OBJECTIVES: To report central corneal thickness (CCT) measurements on patients requesting refractive surgery and to search for possible associations between CCT and patient's origin, age, sex, and preoperative data. SETTING: Department of Ophthalmology, Soroka University Medical Center, and Enaim Refractive Center, Beer-Sheva, Israel. METHODS: Subjects were patients undergoing preoperative examination at our refractive centre during 2003. Patient's age, sex, preoperative CCT, refractive status, keratometry, and intraocular pressure (IOP) were obtained together with country of origin of the patients and their parents. Main outcome measures were CCT measurements and relationship between CCT and patient's origin and preoperative data. RESULTS: A total of 204 patients were included in the study. Patients of North African origin had statistically significantly thinner corneas than patients of other origins (518.9+/-31.5 vs. 545.4+/-30.4 microm in the right eye and 518.4+/-32.1 vs. 546.3+/-29.7 microm in the left eye; P<0.00001). Patients of North African origin were significantly older than patients of other origins (P=0.028). No differences were found when comparing for sex, intraocular pressure, refractive status, and keratometry. When multivariate analysis was performed patient's origin was the only independently associated factor associated with CCT. CONCLUSIONS: This is the first work in reporting lower CCT in people of North African origin examined in a refractive surgery centre. Studies from similar populations are needed to confirm our results.

Thyroid ophthalmopathy.

Thyroid associated ophthalmopathy (TAO) is an inflammatory orbital disease of autoimmune origin with the potential to cause severe functional and psychosocial effects. It presents one of the most difficult challenges in the clinical practice of ophthalmology. Pathogenesis of the disease is not yet fully understood. It is usually associated with thyroid dysfunction. TAO has a variable clinical presentation; it may cause severe damage to vision and orbital architecture. TAO is the most frequent cause of unilateral or bilateral proptosis in adults. Potential sight-threatening complications include optic neuropathy and severe corneal exposure keratopathy. Most patients do not require specific therapy. Those with moderately severe or severe disease are treated with steroids and/or orbital radiation during the inflammatory phase and surgical therapy during the inactive phase. Decompression may be needed in either phase. Although appropriate treatment can restore near normal function and appearance in most cases, the management of TAO is difficult, controversial, and far from optimal. Disease severity is the key determinant of the indication for therapy, while therapeutic choice depends on inflammatory activity. Clinical management is difficult because no immediate or dramatic cure exists. With appropriate medical and surgical treatment, patients can be restored to normal function and appearance in most cases, but the process to reach this goal will usually be lengthy.

Brucella meningitis and papilledema in a child.

PURPOSE: To report a rare case of Brucella meningitis with papilledema in a child and to discuss the findings of neurobrucellosis in children. METHODS: A 6-year-old girl was admitted with headache, fever, and vomiting for 1 week. Her family reported intake of raw unpasteurized goat's milk in the past. Meningeal signs were strongly positive. Bilateral moderate optic disc edema with flame-shaped hemorrhages was observed. RESULTS: The diagnosis of Brucella infection was established by positive blood culture for Brucella species, serum agglutination titer of antibodies to Brucella >1:160, and positive CSF culture. After treatment consisting of trimethoprim-sulfamethoxazole, rifampin, and doxycycline, the patient's condition gradually improved. One month later, the papilledema disappeared. One year after presentation, the patient remains free of symptoms. CONCLUSIONS: Brucella meningitis must be ruled out in symptomatic patients reporting ingestion of raw unpasteurized goat's milk. Papilledema is a frequent clinical feature, but irreversible visual impairment is extremely rare.

Varix of the vortex vein ampulla: a small case series.

PURPOSE: To report three cases of varix of the vortex vein ampulla. METHODS: Observational small case series. During 2002, three patients were examined for suspected choroidal melanoma. In all cases, the lesions were located at the equator or the periphery. RESULTS: The lesions became more prominent when the eyes were positioned in the direction of the lesion, and disappeared when firm pressure by ultrasound probe was applied on the globe, while the eye was in primary position, or fundus was examined with a three-mirror Goldmann contact lens. These dynamic characteristics were also demonstrated by color Doppler imaging. CONCLUSIONS: Varix of the vortex vein ampulla is an extremely rare condition. This diagnosis should be considered when an elevated choroidal lesion disappears when the fundus is examined with contact lens.

Rhodotorula rubra keratitis and melting after repeated penetrating keratoplasty.

PURPOSE: To describe a rare case of Rhodotorula rubra keratitis in a corneal graft, and to discuss the management of this unusual pathogen. METHODS: A 78-year-old debilitated man was treated for corneal abscess and descemetocele in his right eye. Urgent penetrating keratoplasty (PKP) with old donor material was performed. The patient underwent a new PKP when appropriate donor cornea was available. The graft was clear after the operation. Corneal cultures were negative. RESULTS: One month after the second PKP procedure, deep stromal infiltrate with hypopyon appeared. Cultures grew R. rubra. A third PKP operation was performed. Systemic and topical amphotericin B treatment was started. Six months after the last operation the graft remains clear. CONCLUSIONS: Rhodotorula keratitis is an extremely rare infection that should be considered in debilitated patients with persistent and progressive corneal infection despite adequate antibiotic therapy.

Intraocular pressure during haemodialysis: a review.

OBJECTIVES: Although several works in the past have examined the effect of haemodialysis (HD) on intraocular pressure (IOP), reported findings, theories, and conclusions are very different. The objectives of this article are to resume the reported evidence of IOP changes during HD, to review the proposed hypothesis of HD influence on IOP, and to determine if ophthalmic examination is imperative in HD patients. METHODS: We analysed the peer-reviewed English literature and selected all possible relevant articles. RESULTS: The influence of HD on IOP is not clear, and even in recent studies opposite findings can be found. CONCLUSIONS: Future studies are needed to clarify the effects of HD on IOP. In patients with glaucoma or with predisposed narrow angles, or eyes with impaired aqueous outflow, the possibility of acute IOP rise during HD could be much more frequent than in normal patients. So in these patients, a more strict ophthalmic scheduled examination seems to be feasible.

The ocular manifestations of Weissenbacher-Zweymuller syndrome.

PURPOSE: Weissenbacher-Zweymuller syndrome (WZS) is an autosomal recessive disorder of delayed skeletal maturation. Its characteristic features include rhizomelic dwarfism with metaphyseal and vertebral changes. It has been challenged whether WZS is a part of the spectrum of Stickler syndrome. We report ocular findings in the largest ever-presented series of patients with WZS. METHODS: Patients underwent a paediatric examination, including assessment of growth and development, genetic work-up and X-ray of vertebra and long bones. All had a complete ophthalmic examination, cycloplegic refraction, and face and body photography. RESULTS: All patients had hypertelorism and protruding eyes. Four patients had refractive errors necessitating optical correction ranging from +3 to -8 D. Two patients had strabismus. None had vitreoretinal degeneration, glaucoma, or cataract. CONCLUSIONS: Ocular manifestations of WZS differ from those in Stickler syndrome, indicating that the two likely represent distinct clinical entities. Strabismus and various refractive errors often accompany WZS. An ophthalmologist should follow children with this disorder from an early age to prevent amblyopia.

Comparison between clinical and ultrasound findings in patients with vitreous hemorrhage.

PURPOSE: To ascertain the causes of vitreous hemorrhage and to determine the accuracy of ultrasound (U/S) in these cases, based on the degree of agreement between ultrasound and clinical findings. METHODS: A chart review of 96 consecutive patients (106 eyes) with dense vitreous hemorrhage who underwent A- and B-scan U/S by one examiner between June 1996 and June 1999. U/S records were evaluated to determine the presence and exact distribution of areas of retinal detachment and the presence of posterior vitreous detachment, retinal tear, intraocular foreign body, or choroidal detachment. Clinical information was obtained from the medical records after the vitreous hemorrhage was reabsorbed or following vitreous surgery. Clinical and U/S findings were compared. False-positive and False-negative rates for U/S were calculated based on clinical findings. RESULTS: In 37 eyes (35%) the vitreous hemorrhage was because of proliferative diabetic retinopathy and in 33 eyes (31%) because of ocular trauma. The false-positive rate for retinal detachment (retinal detachment by U/S without clinical confirmation) was 18.9% (seven of 37 eyes). Retinal tears were diagnosed and localized accurately in only four of nine eyes (44%). CONCLUSIONS: The most common cause of vitreous hemorrhage was proliferative diabetic retinopathy, followed by ocular trauma. U/S correctly diagnosed all cases of retinal detachment, but less than 50% of retinal tears. A total of 18.9% of the eyes were falsely diagnosed as having retinal detachment. U/S is an effective diagnostic tool in patients with vitreous hemorrhage.

Overexpression of p53 tumor suppressor gene in pterygia.

PURPOSE: To assess p53 gene expression in pterygia with and without recurrence. The pathogenesis of pterygium has not yet been determined. The most widely recognized etiologic factor is ultraviolet radiation, which leads to degeneration of the conjunctiva. However, pterygium was recently found to have several tumor-like characteristics. The p53 gene is a common marker for neoplasia, and is known to control cell cycle, cell differentiation and apoptosis. In this study we examined the expression of the p53 gene in primary pterygia with and without recurrence, searching for the pathogenesis of this very common lesion and for a prognostic factor for recurrence. METHODS: Immunohistochemical staining using a monoclonal antibody to human p53 (DO-7) was performed on 13 consecutive patients with primary pterygia, four pterygia without recurrence and nine pterygia which recurred during a 12-month follow-up. As a control we used two specimens of normal conjunctiva. RESULTS: Seven of the 13 pterygia specimens (54%) were positive for abnormal p53 expression. There was no difference between the groups with and without recurrence. Two out of four pterygia (50%) without recurrence and five out of nine (55.5%) pterygia with recurrence were positive. No pathological staining was observed in the control specimens. CONCLUSIONS: In this study, abnormal p53 expression was found in pterygial epithelium, suggesting that pterygium could be a result of uncontrolled cell proliferation, and not as a degenerative lesion. There seems to be no connection between abnormal p53 expression and recurrence.

Tectonic epikeratoplasty: a surgical procedure for corneal melting.

BACKGROUND AND OBJECTIVE: Tectonic epikeratoplasty (TEK) is a method in which a corneal button, preserved in glycerin is used as a seal over corneal perforation. The graft is sutured to the recipient sclera, upon the sick melted cornea, with silk sutures, after 360 degree peritomy of the conjunctiva. The graft is left in place for a few weeks, and by that time the cornea is completely healed. We describe our experience in TEK as a method of treatment for selected cases of melted cornea or descemetocele. METHODS AND PATIENTS: We review 12 TEK operations done in our department over the period of 1992 to 1997, and describe the outcome in each case. RESULTS: The 12 TEK operations included 9 eyes of 9 patients. The patients, 7 males and 2 females, suffered from ocular surface disturbances including indifference to pain syndrome, Steven-Johnson syndrome, dry eye, relapsing herpetic keratitis, post-traumatic corneal thinning, and local anesthetic abuse. Six of the 9 eyes had leaking perforated corneal ulcer, and the remaining 3 had an imminent perforation caused by descemetocele or melting. All the grafts but one fell off the eyes between 10 and 21 days following surgery. In most of the cases the leakage ceased, and a scar sealing the perforation site was observed. One eye had gone through this procedure 3 times, and another eye had gone through it twice. In only 3 cases did the procedure fail to eliminate leakage, and another TEK or urgent penetrating keratoplasty (PKP) was done. CONCLUSIONS: TEK is an available method for saving the integrity of the globe when PKP is not possible. Although it increases corneal vascularity, PKP can be done later under optimal conditions.

Respiratory arrest and convulsions after peribulbar anesthesia.

We present a case in which a rare and serious complication with respiratory arrest and convulsions occurred after peribulbar anesthesia for cataract surgery. To our knowledge, respiratory arrest has been described as a complication only of retrobulbar, not peribulbar, anesthesia. Anesthesiologists trained in airway maintenance and ventilatory support should be available for immediate help when a peribulbar block is performed.

Retrocorneal membrane after penetrating keratoplasty.

Retrocorneal membranes after penetrating keratoplasty (PKP) is a well known complications, resulting from unintentional retention of the host Descemet's membrane (DM), or donor DM detachment. We describe for the first time the formation of a retrocorneal inflammatory membrane that mimics donor DM detachment or retained recipient DM, and discuss the differential diagnosis of a retrocorneal membrane after PKP. Two patients who underwent PKP and subsequently developed a retrocorneal membrane are described. In both patients' eyes a retrocorneal membrane was observed immediately following penetrating keratoplasty. While the first patient's membrane persisted for 33 months in the presence of a clear graft, the second patient's membrane disintegrated and dissolved within two weeks following treatment with topical steroids. The first case describes a patient with retained Descemet's membrane, while in the second case, it turned out that the retrocorneal membrane was actually an inflammatory membrane.

Toxic effects of subconjunctival 5-fluorouracil and mitomycin C on ciliary body of rats.

PURPOSE: The effects of subconjunctival injection of mitomycin C and different concentrations of 5-fluorouracil on the epithelium of the ciliary body of twenty Sprague Dawley SD rats was studied. METHODS: Twenty rats were divided into four treatment groups. The first three groups received 0.2 ml of 5, 10, and 30 mg of 5-fluorouracil subconjunctivally respectively, and the fourth group 0.2 ml of 0.4 mg/ml mitomycin C subconjunctivally. The right eye received 0.2 ml of the antimetabolite, while the left eye was injected with 0.2 ml of saline subconjunctivally, as a control. The eyes were examined histologically, in a masked fashion, by light and by transmission electron microscopy. In each treatment group, two eyes were examined after one week, and three eyes were examined one month after the subconjunctival injection. RESULTS: Electron microscopy revealed toxic effects in the epithelium of the ciliary body of all treatment groups. The 5-fluorouracil group revealed focal mitochondrial edema, enlargement of intercellular spaces, and dilatation of intracellular spaces. The mitomycin C group showed pyknotic nuclei, enlargement of intercellular spaces, and irregular flattened epithelial cells. The severity of changes correlated with concentration and length of exposure. No pathology was found by light microscopy in all groups. CONCLUSIONS: This study demonstrates that subconjunctival antimetabolites mitomycin C and 5-fluorouracil can penetrate the sclera and exert toxic effects on the epithelium of the ciliary body, even in low doses. These changes were only apparent by electron microscopy and were still present one month after the injection. These findings may contribute to the theory that the application of antimetabolites during or after surgery has a direct effect on the epithelium of the ciliary body, besides its known effect on the conjunctiva. Further studies are needed to evaluate its effect on intraocular pressure.

Eyelid fish-hook injury.

OBJECTIVE: To report a rare case of fish-hook eyelid injury. METHODS: Interventional case-report. A 25-year-old man presented with an upper eyelid fish-hook wound. RESULTS: The hook was extracted under local anaesthesia using the back-out method. Postoperatively, no complications were observed. CONCLUSIONS: In the absence of serious ocular damage, the back-out method seems to be the best option for the removal of the hook in eyelid injuries.