Soluble TNF receptors in vitreoretinal proliferative disease.

PURPOSE: To measure vitreous levels of soluble TNF-receptors (sTNF-Rs) types I and II in eyes with rhegmatogenous retinal detachment (RRD), uncomplicated or complicated with proliferative vitreoretinopathy (PVR), and in eyes with proliferative diabetic retinopathy (PDR). To examine whether there is any relationship between vitreous levels of sTNF-Rs and clinical features of these conditions and between vitreous sTNF-Rs and TNFalpha levels and serum levels of sTNF-RS: METHODS: Vitreous levels of sTNF-Rs and TNFalpha were measured by enzyme-linked immunosorbent assay in 30 eyes with PVR, 30 eyes with uncomplicated RRD, and 29 eyes with PDR. Vitreous from eyes of 10 deceased donors and 9 eyes with macular holes served as control specimens. Serum levels of sTNF-Rs were measured in 17 patients with PDR and 21 patients with PVR. RESULTS: Vitreous levels of sTNF-Rs I and II were increased in eyes with PVR, RRD, and PDR when compared with control eyes (P < 0.002). However, vitreous levels of sTNF-Rs I and II were higher in eyes with PVR than in eyes with RRD (P < 0.01) or PDR (P < 0.03). This contrasted with the findings that serum sTNF-Rs were higher in PDR than in PVR (P < 0.016) and that vitreous levels of TNFalpha were higher in eyes with PDR than in eyes with PVR (P < 0.0005). In PVR, vitreous sTNF-Rs levels were associated with the duration of retinal detachment, number of previous external operations, and grade of severity, whereas in PDR these levels were not related to the type or duration of diabetes or its complication with traction retinal detachment. CONCLUSIONS: These observations suggest the existence of TNF inhibitory mechanisms within the eye during retinal processes of inflammation and angiogenesis. That high vitreous levels of sTNF-Rs relate to severity of retinopathy suggests that these molecules may constitute reactive products of inflammation. Effective control of TNFalpha activity by sTNF-Rs within the retinal microenvironment may determine the outcome and severity of retinal proliferative conditions.

Eye injuries in the U.S. Armed Forces.

OBJECTIVE: To develop prevention and treatment modalities for eye injuries, ophthalmologists require epidemiological data on the various types of eye injuries. This study sought to define eye injury patterns in the U.S. armed forces. METHOD: Data on patterns of eye injury in the armed forces were obtained through voluntary reporting by U.S. military ophthalmologists throughout the world. The reporting format was standardized with the U.S. Eye Injury Registry initial and follow-up report forms. The data were analyzed for significant injury patterns. RESULTS: Data on 112 patients were submitted, representing a broad range of the military population. Data on a total of 96 patients with a 6-month follow-up were analyzed in this study. Immediately after injury, 43% of the patients were noted to have poor vision (worse than 20/200). After treatment, only 20% were noted to have poor vision. Patients lost an average of 21.6 days of work after a severe eye injury. CONCLUSION: An eye injury is a traumatic and potentially debilitating event. The loss of visual acuity can be drastic, resulting in an extensive recovery period.

Eye injuries in a terrorist bombing: Dhahran, Saudi Arabia, June 25, 1996.

OBJECTIVE: We report the experience of our institution in the evaluation and care of multiple simultaneous ocular trauma patients after a terrorist bomb attack on a United States military base in Saudi Arabia. DESIGN: Retrospective, noncomparative small case series. PARTICIPANTS: Three patients who received severe ocular injuries after a terrorist bombing. INTERVENTION: All patients underwent surgical repair of the injuries that were inflicted as a result of the terrorist bombing. MAIN OUTCOME MEASURES: Baseline ocular characteristics, intraoperative findings, surgical procedures, and final (3 years after injury) anatomic and visual outcomes were noted. RESULTS: Glass fragments caused by the blast were the mechanism of all the ocular injuries in these patients. All patients had primary repair of the injuries done in Saudi Arabia and were sent to our institution for tertiary care. Three of the four eyes injured had stable or improved visual acuity and one eye was enucleated. Two patients had no serious injury other than the globe trauma. One patient had extensive eyelid trauma and required serial procedures to allow fitting of a prosthesis. CONCLUSIONS: Blast-injury patients are at risk for open globe injury as a result of glass fragments. The types of injury that can occur from terrorist blasts can be extensive and involve all the tissues of the eye, the ocular adnexa, and the orbit.

Outcome of sulcus fixation of dislocated posterior chamber intraocular lenses using temporary externalization of the haptics.

OBJECTIVE: This study evaluated the visual outcome and complications of repositioning and sulcus fixation of a dislocated posterior chamber intraocular lens (PC IOL) using a technique in which the haptics of the IOL are temporarily externalized for suture placement. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Seventy-eight patients with a dislocated PC IOL. INTERVENTION: All patients underwent surgery to fixate the PC IOL using this technique. MAIN OUTCOME MEASURES: Patients were evaluated for visual acuity, refractive error, and surgical complications associated with the procedure. RESULTS: The average visual acuity before surgery was 20/205 (range, 20/20 to light perception), with a median refractive error of -1.00 diopters (D; range, -7.25-+15.00 D). After surgery, the average visual acuity improved to 20/72 (range, 20/20 to no light perception), with a median refractive error of -0.75 D (range, -5.50-+3.50 D). Patients were observed for a median of 15.5 months (range, 6-57 months). Twenty patients had postoperative cystoid macular edema (26%), 7 patients had an epiretinal membrane (ERM) (9%), and 5 patients had a retinal detachment (6%). Eight patients (10%) experienced iris capture of the sutured IOL, and in three patients (4%) the PC IOL dislocated again after surgery. CONCLUSIONS: This technique is an effective method for securing a dislocated PC IOL.

Vascular adhesion molecules in vitreous from eyes with proliferative diabetic retinopathy.

PURPOSE: To investigate whether proliferative vitreoretinopathy (PDR) is associated with a selective increase in vitreous levels of soluble vascular cell adhesion molecules that mediate leukocyte extravasation and interaction with endothelium during processes of inflammation and neovascularization. METHODS: Vitreous from 55 patients undergoing vitrectomy for treatment of PDR complicated by vitreous hemorrhage and/or traction retinal detachment was assayed for the presence of the soluble vascular cell adhesion molecules sICAM-1, sVCAM-1, and sE-selectin using a standard enzyme-linked immunosorbent assays (ELISA). Vitreous from 12 cadaveric eyes matching age and sex of the patients were used as control samples. RESULTS: Vitreous levels of sICAM-1, sVCAM-1, and sE-selectin were significantly higher in eyes with PDR than in control cadaveric vitreous, and levels of all three molecules did not relate to the type or duration of diabetes mellitus. However, eyes with either traction retinal detachment alone or both traction retinal detachment and vitreous hemorrhage exhibited significantly higher levels of sICAM-1 and sE-selectin than eyes with vitreous hemorrhage alone. Vitreous levels of sVCAM-1 were similar in eyes with either vitreous hemorrhage or traction retinal detachment alone. CONCLUSIONS: The present observations suggest that molecular inflammatory mechanisms may contribute to processes of neovascularization and fibrosis observed in PDR, possibly not as the causative event, but as a result of endothelial, Müller, and retinal pigment epithelial cell activation. The results also indicate that retinal detachment amplifies the existing inflammation within the diabetic retina. Identification of any abnormalities in the production and control of specific adhesion molecules could have important implications in the design of new therapeutic regimens to treat and prevent this sight-threatening complication of diabetes mellitus.

Evidence for control of tumour necrosis factor-alpha (TNF-alpha) activity by TNF receptors in patients with proliferative diabetic retinopathy.

TNF-alpha has been implicated in the pathogenesis of insulin- dependent diabetes mellitus (IDDM). At present there are no studies linking serum levels of soluble TNF receptors (sTNF-R) to the development of diabetic microvascular complications such as proliferative diabetic retinopathy (PDR), or to the production of TNF-alpha in these patients. We investigated serum levels of sTNF receptors (sTNF-RI and sTNF-RII) in IDDM patients with or without PDR, and related these to the in vitro production of TNF-alpha upon activation of whole blood and isolated mononuclear cells (MNC). We observed higher serum levels of sTNF-RI in IDDM patients with active (range 945-6630 pg/ml; P = 0.029) or quiescent PDR (range 1675-4970 pg/ml; P = 0.00092) than in individuals with IDDM without retinopathy (range 657-2617 pg/ml) or healthy controls (range 710-1819 pg/ml; P = 0.0092 and 0.0023, respectively). Increased serum levels of sTNF-RII were also seen in IDDM patients with active PDR (range 1749-5218 pg/ml; P = 0.034) or quiescent PDR (range 1494-5249 pg/ml; P = 0.0084) when compared with disease controls (range 1259-4210 pg/ml) or healthy subjects (range 1237-4283 pg/ml). Whole blood production of biologically active TNF-alpha was lower in PDR patients than in disease (P = 0.04) and healthy controls (P < 0.005), contrasting with a higher production of TNF-alpha by lipopolysaccharide (LPS)-activated MNC from PDR patients (P = 0.013). Inhibition of TNF-alpha by TNF-R in plasma supernatants of activated blood from PDR patients was demonstrated by increase of TNF-alpha activity in the presence of anti-TNF-RI and anti-TNF-RII antibodies. These observations suggest that abnormalities in TNF-alpha production and control may operate during the development of microvascular complications of diabetes mellitus.

Ocular injuries from paintball pellets.

OBJECTIVE: To evaluate the ocular effects of blunt trauma due to injury from a paintball pellet. DESIGN: Noncomparative case series. PARTICIPANTS: Thirteen patients who suffered ocular injury from paintballs are described. The patients presented to six different civilian and military emergency departments in tertiary care medical centers. INTERVENTION: Patients were treated for the ocular injury. MAIN OUTCOME MEASURES: Patients were evaluated for initial and final visual acuity. The reason for persistent loss of vision was delineated. RESULTS: There were 12 males and 1 female with an average age of 21 years (range, 12-33 years). Eleven of the 13 had no ocular protection at the time of the ocular injury. On initial examination, nine patients had a hyphema, nine had a vitreous hemorrhage, six had a retinal tear or detachment, three had corneal or corneal-scleral ruptures, and one had traumatic optic neuropathy. The final visual acuity was 20/40 or better in two patients, 20/50 to 20/150 in three patients, and 20/200 or worse in eight patients. CONCLUSION: Injuries due to paintball pellets can result in severe ocular damage and significant loss of vision. Eyecare professionals should be aware of the risks of this sport and must strongly advise participants to wear adequate protection when involved in this activity.

Expression of hematopoietic cell markers by retinal pigment epithelial cells.

PURPOSE: We investigated the expression of various isoforms of the hematopoietic cell marker CD45 on retinal pigment epithelial cells in relation to their expression of CD68 and the cytokine-reactive intercellular adhesion molecule-1 (ICAM-1). We also determined the effect of the pro-inflammatory cytokines IL-1 beta, TNF alpha and IFN gamma on the expression of these molecules by RPE cells in culture. METHODS: Monolayers of RPE cells between 3rd and 7th passages were cultured in the presence or absence of cytokines, followed by immunohistochemical staining for CD45 (170-220 kD), CD45RA (205 and 220 kD), CD45RO (180 kD), CD68 and ICAM-1, using the alkaline phosphatase-anti-alkaline phosphatase (APAAP) technique. Total (membrane and cytoplasmic) expression of each of the three CD45 isoforms was determined by enzyme-linked immunoassays (ELISA). RESULTS: The majority of RPE cells expressed all isoforms of CD45 on their membranes and the pattern of expression of these molecules was not modified by culture. The greatest intensity of membrane staining was consistently observed with antibodies to CD45RA (205 + 220 kD), while CD45 (170-220 kD) showed to be the predominant isoform within the whole cell, as judged by ELISA assays. Unlike the membrane expression of CD45, only 20% of RPE cells stained for the macrophage surface molecule CD68 following 4 h of culture, but progressive increase in the proportion of CD68 positive cells was observed by extending the culture to 24 and 48 h. Neither the expression of CD68 nor the various isoforms of CD45 were modified by incubation with pro-inflammatory cytokines. Staining for ICAM-1 was observed in 21-25% of RPE cells throughout the 48 h culture. However, incubation with 50 pg/ml of IL-1 beta, TNF alpha and IFN gamma caused a marked increase in the RPE cell expression of ICAM-1 following 4, 24 and 48 h culture. CONCLUSIONS: The observations suggest that hematopoietic cell markers are constitutively expressed on RPE cells and that functions governed by these molecules are not influenced by pro-inflammatory signals. Expression of hematopoietic molecules by RPE cells may influence the macrophage-like properties of these cells and may also aid in the identification of RPE cells during pathological processes, particularly in the proliferative retinopathies, where these cells undergo phenotypic and functional changes.

Dissection along the optic nerve axis by a BB.

A 13-year-old Hispanic boy suffered a perforating injury to his right eye from a BB. The clinical examination and computed tomographic scan revealed questionable light perception and a dense foreign body, consistent with a BB, situated behind the globe. A vitrectomy was performed that was unsuccessful. Six months later the eye was enucleated, and the BB was found to be within the optic nerve sheath. Foreign bodies within the optic nerve are uncommon. The foreign body in this case, a BB, entered the optic nerve through the nerve head after traversing the globe. The histopathologic findings in this unusual case are presented herein.

Intercellular adhesion molecule-1 in proliferative vitreoretinopathy.

PURPOSE: To measure vitreous levels of the soluble intercellular adhesion molecule (sICAM-1) in eyes with rhegmatogenous retinal detachment (RRD) complicated or uncomplicated by proliferative vitreoretinopathy (PVR) to investigate whether levels of this molecule related to history of previous retinal surgery or to the duration and severity of PVR. METHODS: The authors measured vitreous sICAM-1 by enzyme-linked immunosorbent assay in 28 eyes with PVR and 35 eyes with uncomplicated RRD. Vitreous from 10 eyes with macular holes and from 12 cadaveric eye donors were used as control specimens. RESULTS: Vitreous sICAM-1 levels were higher in the group with RRD complicated by PVR as a whole than in the group with RRD alone or in the control groups. In patients with no previous retinal surgery, there was no difference in vitreous sICAM-1 levels between the groups with RRD alone and RRD complicated by PVR. However, in patients who had undergone previous external surgery, those with PVR showed higher levels of vitreous sICAM-1 than those with RRD alone. In PVR, raised levels of sICAM-1 were associated preferentially with a history of previous vitrectomy as well as with a longer duration of the condition, although these levels were not related to the grade of PVR. In eyes with RRD alone, the levels of sICAM-1 were not enhanced with the duration of the detachment. Despite showing high vitreous levels of sICAM-1, patients with PVR did not exhibit increased serum levels of this adhesion molecule. CONCLUSIONS: The current observations suggest that those persons in whom PVR develops may have an impairment of the mechanisms that control the inflammatory response to retinal trauma. Persistently raised vitreous levels of sICAM-1 point to the continued operation of cytokine-mediated vascular reactions at the blood-retinal barrier.

Development of an enzyme-mediated assay for phenylalanine in blood spots.

We describe the optimization of a rapid procedure for the elution of phenylalanine from blood spots and the estimation of the amino acid eluted using an enzyme-mediated assay linked to a colorimetric detection system. The method is rapid, fully quantitative, interference-free, accurate and precise unlike many of the methods currently employed for phenylalanine determination. The performance of the proposed method may necessitate the review of reference ranges and cut-off assignment strategies.