Cyclitic Membrane Formation Research Articles

Histopathology of Streptococcus Mitis/Oralis Endophthalmitis after Intravitreal Injection with Bevacizumab

To report the histopathologic findings of a series of patients from an outbreak of Streptococcal endophthalmitis after intravitreal injection of bevacizumab prepared by a single compounding pharmacy. Case series. Seven surgical specimens (5 enucleated globes and 2 evisceration specimens) from 7 patients with endophthalmitis after intravitreal injection of bevacizumab. Retrospective case series, including clinical data and histopathologic specimens examined by light microscopy. Review of clinical data included baseline visual acuity, clinical intervention, and time elapsed from injection to loss of globe. Histopathologic specimens were reviewed for pathologic changes at all tissue levels. Seven of 12 total patients (4 women, 3 men; mean age, 77.7 years) from an outbreak of Streptococcus mitis/oralis endophthalmitis after bevacizumab injection ultimately sustained loss of the affected globe, with an average of 139.1 days elapsed between injection and globe loss. Mean time from injection to presentation was 2.86 days (range, 1-6), and all patients were initially treated with vitreous tap and injection. Although histologic review of surgical specimens disclosed a wide range of pathologic tissue changes, recurring patterns of tissue damage were evident. All 5 enucleated globes displayed retinal detachment, fibrous proliferation with cyclitic membrane formation, rubeosis iridis, and secondary angle closure. All 7 specimens displayed persistent choroidal inflammation, in 1 case 208 days after injection. Six of 7 specimens had foci of retinal necrosis. Although vitreous cultures were positive in all cases, no organisms were identified by light microscopy in any of the 7 specimens. S.mitis/oralis endophthalmitis is a devastating complication of intravitreal injection with bevacizumab with a high rate of globe loss (7 of 12 patients, 58.3%) and a wide variety of severe pathologic tissue changes. Although no organisms were identified in the examined tissues, persistent inflammation was present in all cases, and fibrous proliferation resulted in cyclitic membrane formation and retinal detachment in all enucleated globes. These findings suggest that potential globe-salvaging interventions must address a pattern of changes involving persistent, chronic inflammation and fibrovascular proliferation as key components.

Histopathology of Behçet’s uveitis

AbstractPurpose To report the histological findings in an eye with severe Behçet’s disease.Methods A 17‐year‐old male had a longstanding history of chronic intraocular inflammation, which was treated with high dose steroids, immunosuppression and biological agents (anti‐TNF therapy). Despite this aggressive treatment, he suffered persistent uveitis, and had also undergone cataract and pars plana vitrectomy with silicone oil tamponade. Eventually the patient underwent enucleation of his left eye, which had become blind and painful. The specimen was sent to the Pathology Dept. RLBUHT, for morphological examination.Results Histological sections of the enucleated eye demonstrated extensive pathological changes. These included: chronic keratitis with associated neovascularisation; severe chronic granulomatous iridocyclitis with the development of anterior synechiae with angle closure, as well as extensive posterior cyclitic membrane formation with ciliary process destruction. The inflammation, which was characterised by dense lymphocytic and plasma cell infiltrates, extended posteriorly into the choroid, focally involving the retina. Chronic vasculitis resulted in a typical “onion‐skinning” appearance of some blood vessels. There was optic disc cupping. Immunohistochemistry was performed to characterise the lymphocytic and plasma cell populations.Conclusion This case is a rare example of end‐stage Behçet’s disease in which the histopathological alterations will be demonstrated.

Authors′ reply

Dear Editor, We thank Azad et al. for showing interest in our article.1 As this child needed immediate intervention to save the eye and prevent phthisis bulbi, a formal institutional review board approval was not possible as it would have taken at least a few months. The principal concern was potential altered vasculogenesis in the treated eye and other organs. But as the avascular retina was well ablated, we believe it safer to inject bevacizumab (Avastin) in this situation rather than as primary therapy in an eye with viable peripheral retina. With this background in the face of an eye that was rapidly deteriorating to cyclitic membrane formation and phthisis the authors considered the potential benefits and harmful side effects of intravitreal bevacizumab. The parents received extensive councelling regarding potential complications of bevacizumab including possible retarded growth or maldevelopment of other organs Aggressive posterior retinopathy of prematurity (ROP) is now a distinct category of ROP which has been published2 and does not need further elaboration. The disease was symmetrical in both the eyes. There was no tunica vasculosa lentis seen prior to laser and iris neovascularization, hypotony, cataract and corneal clouding appeared after the ablative procedure. Given these features, anterior segment ischemia was the most likely diagnosis. Without prompt intervention, the eye would have likely progressed quickly to irreversible phthisis. Ocular hypotony due to scleral indentation is a consideration but typically this will be a transient phenomenon that typically would resolve with anti-inflammatory and cycloplegics therapy. It would typically occur within a day or two of laser rather than at one week's time. Our post-operative examination revealed no obvious choroidal effusion. With a dramatically worsening clinical course after three days of topical steroids and cycloplegics, we believed that systemic steroids would not help much and could add to the complications. Moreover, use of high dose systemic steroids is ill advised in neonates because of potential growth retardation, adrenal suppression and hypertension. We have used systemic steroids on a series of patients with aggressive ROP and noted minimal ocular benefit. Most authorities in pediatric rheumatology recommend keeping the dose of steroids below 1 mg per kg body weight. In these children that dose is not enough to impact the severe proliferative and inflammatory response. To avoid complications like anterior segment ischemia, previous studies3 have suggested to perform scatter laser in the horizontal meridians, to do laser in multiple sittings (but both these would increase the risk of retinal detachment), to use less power while treating these meridians and to use cryo instead of laser as freezing causes less damage to the ocular vessels. But this should not discourage the treating surgeon from being aggressive in the treatment of ROP. We have shown improved visual and anatomic outcomes with early and thorough treatment.4 Anterior neovascularization, anterior fibrovascular proliferation and hypotony prompted us to the diagnosis of anterior segment ischemia. Iris atrophy and cataract were also seen to develop later, which also are consistent with anterior segment ischemia. There was likely an element of inflammation also but we felt ischemia was the predominant mechanism. We too have a lot of reservations about injecting a drug like bevacizumab, in a premature child, and recommend that it only be used in carefully monitored trials or as a lat resort in advanced cases. In this precious neonate who was certainly going to lose an eye, we believe that there was no better alternative available and all standard treatments were exhausted. The parents gave a detailed informed consent for this intervention with the understanding of potential risks, and the outcome was favorable.

Phacoanaphylaxis in Behçet's disease: A clinicopathologic and immunohistochemical study

Purpose To describe the occurrence of phacoanaphylaxis in enucleated eyes of patients with Behçet's disease. Design Retrospective, observational, case series and human tissue study. Participants Twenty-six patients with Behçet's disease who underwent enucleation. Methods Histopathologic analysis was performed on 28 enucleated eyes of 26 patients with Behçet's disease. The eyes were divided into two groups, based on the absence or presence of tractional retinal detachment associated with cyclitic membrane formation. Selected eyes with tractional retinal detachment were stained for immunohistochemical examination. Main outcome measures Histopathologic examination of enucleated eyes, including routine histopathologic and immunohistochemical studies. Results None of the five eyes without retinal detachment showed phacoanaphylaxis. Nine of the 23 eyes with detachment exhibited phacoanaphylaxis, 10 showed no inflammation of the lens, and four were aphakic. There was marked inflammatory cell infiltration in the cyclitic membrane of all nine eyes with phacoanaphylaxis. Immunohistochemical examination demonstrated positive staining for the macrophage markers in the epithelioid and giant cells. The average interval between onset of the ocular manifestations of Behçet's disease and enucleation was 63 months for eyes with phacoanaphylaxis and 35 months for eyes without phacoanaphylaxis ( P<0.005). Conclusions In Behçet's disease, eyes with long-standing intraocular inflammation complicated by cyclitic membrane formation may develop phacoanaphylaxis. Such patients may benefit from surgical removal of the cyclitic membrane along with the lens in eyes with significant visual function.

Retinal detachment and phthisis bulbi after implantation of an iris prosthetic system

We report 2 eyes of 2 patients who developed persistent inflammation, hypotony, and total retinal detachment after secondary implantation of an iris prosthetic system (IPS) in association with cataract surgery. The first patient had an uneventful history of 16 years despite a retained intraocular glass foreign body and the second patient, of 38 years after sustaining penetrating corneoscleral injury with iris tissue loss. Both patients were thoroughly assessed clinically, and the enucleated globe in the first patient was examined by light microscopy. Both eyes had chronic inflammation with retrocorneal and cyclitic membrane formation around the artificial iris–lens diaphragm. These cases suggest that implantation of an IPS combined with cataract surgery can trigger decompensation of posttraumatic eyes that had been stable over a long period.

Incising the Thick Retrolental Fibrovascular Tissue With a Hooked Sclerotome in Persistent Hyperplastic Primary Vitreous

A technique for incising thick retrolental fibrovascular tissue and extensive cyclitic membrane is reported in a case of anterior persistent hyperplastic primary vitreous. A membranectomy was performed in a 1-month-old post-lensectomy baby via a limbal approach. A sclerotome tip was hooked to cut through an extremely thick fibrovascular tissue by rotating the sclerotome by its grip. Sutherland microscissors (Grieshaber, Switzerland) and a vitrectomy cutter were used for further membranectomy. The baby was followed-up until age 18 months. A total of 3 membranectomy sessions were required because of rapid cyclitic membrane formation, severe centripetal retraction of the membrane on the ciliary processes, and posterior synechia. Thorough membranectomy and cutting the iris edge maintained a clear pupillary area during the 13-month postoperative period. Extremely thick retrolental fibrovascular tissue is a challenging condition that can be dealt with by delicate instrumentation.

Non-invasive methods to evaluate the blood-aqueous barrier function

We used vitreous fluorophotometry to supplement standard clinical techniques and fluorescein angiography to study 23 eyes in 12 patients with pars planitis. All eyes leaked abnormal amounts of fluorescein into the vitreous. The leakage was generalized in the posterior segment of the eye. In milder cases, leakage was greater posteriorly; more severe cases showed preferential leakage from the equatorial and midperipheral regions.There was no predilection for leakage in the inferior fundus. The eyes in which greater leakage occurred inferiorly tended to be those with greater overall leakage; all but one involved early cyclitic membrane formation or heavy neovascularization of the pars plana membrane.The amount of cystoid macular edema demonstrated by fluorescein angiography correlated well with vitreous fluorophotometric values, as did vitreous haze, the extent and density of the inferior membrane, and visual acuity.

Vitreous Fluorophotometry in Pars Planitis

We used vitreous fluorophotometry to supplement standard clinical techniques and fluorescein angiography to study 23 eyes in 12 patients with pars planitis. All eyes leaked abnormal amounts of fluorescein into the vitreous. The leakage was generalized in the posterior segment of the eye. In milder cases, leakage was greater posteriorly; more severe cases showed preferential leakage from the equatorial and midperipheral regions. There was no predilection for leakage in the inferior fundus. The eyes in which greater leakage occurred inferiorly tended to be those with greater overall leakage; all but one involved early cyclitic membrane formation or heavy neovascularization of the pars plana membrane. The amount of cystoid macular edema demonstrated by fluorescein angiography correlated well with vitreous fluorophotometric values, as did vitreous haze, the extent and density of the inferior membrane, and visual acuity.

Vitrectomy Techniques in the Management of Selected Penetrating Ocular Injuries

Closed vitrectomy techniques provide new capabilities to treat severe penetrating ocular injuries involving posterior segment structures. With these methods damaged iris tissue, lens, and vitreous can be removed and intraocular opacities can be cleared to identify and treat any retinal damage. Removal of damaged vitreous also prevents later cyclitic membrane formation and traction on the retina. The vitrectomy technique can be combined with additional methods to treat other conditions including nonmagnetic intraocular foreign bodies. We present the rationale and technique of vitrectomy together with the results of treatment in 51 consecutive cases of penetrating ocular trauma. Guidelines are offered for management of severe penetrating injuries.