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Posterior lens capsular neovascularization of young: management using endodiathermy assisted biopsy

      Neovascularization of lens capsule has so far been described in cases of retinal detachment or proliferative diabetic retinopathy in pseudophakes.
      • Aiello L.P.
      • Avery R.L.
      • Arrigg P.G.
      • et al.
      Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders.
      • Eren E.
      • Küçükerdönmez C.
      • Yilmaz G.
      • Akova Y.A.
      Regression of neovascular posterior capsule vessels by intravitreal bevacizumab.
      • Comarrata M.R.
      • Chang S.
      • Sparrow J.
      Iris neovascularization in proliferative vitreoretinopathy.
      • Barile G.R.
      • Chang S.
      • Horowitz J.D.
      • et al.
      Neovascular complications associated with rubeosis iridis and peripheral retinal detachment after retinal detachment surgery.
      We hereby describe a unique case that presented with posterior lens capsular neovascularization in the absence of any other sign of anterior segment neovascularization, and it was found to be associated with idiopathic ciliary body inflammation. The management with regard to clearing of the visual axis, biopsy of the involved tissue, and follow-up is described.
      A 25-year-old male presented with history of gradually progressive diminution of vision in right eye with visual acuity (VA) of 20/40 OD and 20/20 OS. On examination, the patient was found to have a vascularized membrane over the posterior aspect of the lens capsule. There was no evidence of retrolental or anterior chamber cells on slit-lamp biomicroscopy. On indirect ophthalmoscopy, fundus was normal. Patient at 1-month follow-up was found to have a further decline in vision to 20/80. The posterior lens capsular membrane had progressed, and fine blood vessels arose nasally behind the lens capsule with progressive branching (Fig. 1A). Neovascularization of angle, iris, or retina was absent clinically. Fundus fluorescein angiography ruled out peripheral retinal ischemia. Ultrasound biomicroscopy (Sonomed Escalon, Lake Success, N.Y.) showed significant ciliary body thickening (from 8–12 clock-hours) when compared with other regions within the same eye and the fellow eye (Fig. 2A). The area of ciliary body thickening corresponded to the region from where neovascularization of lens capsule (NVC) appeared to originate. Magnetic resonance imaging of the right orbit showed significant and similar ciliary body thickening along with contrast enhancement within the ciliary body and the lens capsule, suggestive of an inflammatory cause (Fig. 3). Blood counts of the patient were within normal limits, and erythrocyte sedimentation rate was 12 mm. Mantoux test was normal, and contrast-enhanced CT chest did not show any evidence of lymphadenopathy or lung parenchymal pathology.
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      Fig. 1Anterior segment photograph shows (A) a vascularized membrane over the posterior lens capsule. (B) Posterior chamber intraocular lens in sulcus with endothelial cell precipitates and anterior chamber reaction seen at third post operative day.
      Figure thumbnail gr2
      Fig. 2A, Ultrabiomicroscopy shows a grossly thickened ciliary body (thick arrow), which is merged with anterior and posterior zonular complex (thin arrow) and conjoined with the posterior capsule, which can also be appreciated as a thickened band (star). B, Ultrabiomicroscopy shows posterior chamber intraocular lens well placed in the sulcus over the thickened posterior capsular edges (star). Note that the ciliary body thickening has diminished but is still adjoined with the zonular complex (arrow).
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      Fig. 3Magnetic resonance imaging axial scan showing contrast enhancement along the ciliary body and posterior lens capsule in the right eye.
      In view of progressive membrane growth and significant diminution of vision, surgical intervention was planned. Direct ciliary body biopsy was not performed because of the risk of intraocular hemorrhage and difficulty in determining exact depth of penetration and localization of the lesion.
      Instead, posterior lens capsular biopsy was performed to gain indirect histopathologic evidence to enable diagnosis of ciliary body lesion. Cataract surgery by routine phacoemulsification was performed. As an alternative to Fugo plasma blade, unipolar endodiathermy was used to cauterize the vessels permeating the central 6-mm zone. Central posterior capsulotomy was performed using 25G vitreoretinal scissors followed by limited anterior vitrectomy (Infiniti; Alcon Laboratories Inc). The 3-piece acrylic hydrophobic foldable intraocular lens (MA60AC; Alcon, Fort Worth, Texas) was implanted in sulcus and the posterior capsule specimen thus obtained was sent for histopathology. Biopsy revealed proliferative loose fibrous tissue without any evidence of pleomorphism suggestive of a non-neoplastic pathology (Fig. 4). No granulomas were identified. The section was stained for Gram staining, acid-fast bacilli, S-100, and HMB-45 to rule out neural or melanoma phenotype; all stains were found to be negative. On the third postoperative day, the patient presented with large cellular precipitates in anterior chamber and on corneal endothelium (Fig. 1B). Anterior chamber tap was done with aspiration of cells, and cytologic analysis showed nonspecific inflammatory cells with HMB-45 immunostaining for melanoma to be negative. The corneal endothelial precipitates resolved with a course of topical steroids and VA improved to 20/20. After 3 months of tapering steroids, the patient had a mild anterior chamber reaction for which he has been kept on low-dose steroids. A repeat ultrabiomicroscopy showed resolution of ciliary body thickening with no reaction in anterior chamber at 6-month follow-up (Fig. 2B). He developed a retro-IOL membrane 8 months postoperatively for which Nd:YAG laser capsulotomy was performed.
      Figure thumbnail gr4
      Fig. 4A, Low-power view of posterior capsular tissue shows proliferating fibrous tissue. Original magnification ×100. B, Higher magnification to show lack of pleomorphism in these spindle-shaped cells. Original magnification ×200. Hematoxylin and eosin staining.
      Anterior ocular neovascularization usually develops in eyes with chronic posterior segment ischemia, long-standing peripheral retinal detachment, or proliferative vitreoretinopathy as a result of exposure to vascular endothelial growth factor (VEGF), which follows its concentration gradient from vitreous to anterior segment.
      • Comarrata M.R.
      • Chang S.
      • Sparrow J.
      Iris neovascularization in proliferative vitreoretinopathy.
      • Barile G.R.
      • Chang S.
      • Horowitz J.D.
      • et al.
      Neovascular complications associated with rubeosis iridis and peripheral retinal detachment after retinal detachment surgery.
      We had previously described NVC in a phakic eye without neovascularization of iris or angle, but in the presence of old retinal detachment.
      • Gupta S.
      • Gogia V.
      • Ramya A.
      • Sihota R.
      Capsular neovascularisation: case report and review of literature.
      The present case experienced NVC in the absence of any recognised risk factor for neovascularization.
      Ciliary body thickening is usually seen in cases with uveitis, a condition that is accompanied by anterior chamber and/or retrolental cells in the acute and chronic phases. However, our patient had localized ciliary body thickening, probably suggesting the occurrence of an undefined pathology that predominantly involved ciliary body without adjacent vitreal involvement or anterior spillover. Prostaglandins involved in intraocular inflammation mediate release of matrix metalloproteinase enzymes (matrix metalloproteinases 1–3), which are involved in the extracellular matrix degradation.
      • Kulkarni P.S.
      The role of endogenous eicosanoids in rabbit-intraocular inflammation.
      • Nagase H.
      • Fields G.B.
      Human matrix metalloproteinase specificity studies using collagen sequence-based synthetic peptides.
      We hypothesize that this probably led to microbreach of the lens capsule, which lay adjacent to the inflamed ciliary body, thus aiding sequestration of the inflamed mediators into the lens substance. Uveitis per se is known to increase the concentration of intraocular VEGF, which may not act as an angiogenic stimulator in cases of anterior uveitis; however, it may do so when exposed to intralenticular environment.
      • Paroli M.P.
      • Teodori C.
      • D’Alessandro M.
      • Mariani P.
      • Iannucci G.
      • Paroli M.
      Increased vascular endothelial growth factor levels in aqueous humor and serum of patients with quiescent uveitis.
      Lens capsule secretes antiendothelial cell inhibitory factors that inhibit NVC even in the presence of concurrent iris neovascularization. Any injury allows the lens capsule to respond to lens-specific growth factors. The heparin-sulfate proteoglycans that are expressed by the lens capsule act as a potential reservoir of VEGF188 isoform to permit proliferation of new vessels.
      • Ash J.D.
      • Overbeek P.A.
      Lens-specific VEGF A expression induces angioblast migration and proliferation and stimulates angiogenic remodeling.
      • Williams G.A.
      • Eisenstein R.
      • Schumacher B.
      • Hsiao K.C.
      • Grant D.
      Inhibitor of vascular endothelial cell growth in the lens.
      • Rutland C.S.
      • Mitchell C.A.
      • Nasir M.
      • Konerding M.A.
      • Drexler H.C.A.
      Microphthalmia, persistent hyperplastic hyaloid vasculature and lens anomalies following overexpression of VEGF-A188 from the αA-crystallin promoter.
      Thus, all these factors in combination may have led to this presentation.
      Phacoemulsification along with posterior capsulotomy in this case represents a rare example wherein indirect evidence of histopathology of ciliary body lesion was the goal. Lens capsular biopsy was obtained in a relatively noninvasive manner. The application of cautery promoted blood vessel coagulation and prevented untoward complications such as hyphema and vitreous hemorrhage. Follow-up helped establish the benign nature of this lesion as the ciliary body thickness regressed along with significant improvement in VA, as well as media haze over time. However, the patient had continuing inflammation, as evidenced by the presence of retro-IOL membrane and anterior chamber reaction. To the best of our knowledge, this case is the first of its kind in which ciliary body inflammation manifested as posterior capsular neovascularization along with opacification, and biopsy of the capsule obtained with the help of endodiathermy-assisted cauterization provided an indirect assessment of ciliary body mass.

      References

        • Aiello L.P.
        • Avery R.L.
        • Arrigg P.G.
        • et al.
        Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders.
        N Engl J Med. 1994; 331: 1480-1487
        • Eren E.
        • Küçükerdönmez C.
        • Yilmaz G.
        • Akova Y.A.
        Regression of neovascular posterior capsule vessels by intravitreal bevacizumab.
        J Cataract Refract Surg. 2007; 33: 1113-1115
        • Comarrata M.R.
        • Chang S.
        • Sparrow J.
        Iris neovascularization in proliferative vitreoretinopathy.
        Ophthalmology. 1992; 99: 898-905
        • Barile G.R.
        • Chang S.
        • Horowitz J.D.
        • et al.
        Neovascular complications associated with rubeosis iridis and peripheral retinal detachment after retinal detachment surgery.
        Am J Ophthalmol. 1998; 126: 379-389
        • Gupta S.
        • Gogia V.
        • Ramya A.
        • Sihota R.
        Capsular neovascularisation: case report and review of literature.
        Eye (Lond). 2014; 28: 358-359
        • Kulkarni P.S.
        The role of endogenous eicosanoids in rabbit-intraocular inflammation.
        J Ocul Pharmacol. 1991; 7: 227-241
        • Nagase H.
        • Fields G.B.
        Human matrix metalloproteinase specificity studies using collagen sequence-based synthetic peptides.
        Biopolymers. 1996; 40: 399-416
        • Paroli M.P.
        • Teodori C.
        • D’Alessandro M.
        • Mariani P.
        • Iannucci G.
        • Paroli M.
        Increased vascular endothelial growth factor levels in aqueous humor and serum of patients with quiescent uveitis.
        Eur J Ophthalmol. 2007; 17: 938-942
        • Ash J.D.
        • Overbeek P.A.
        Lens-specific VEGF A expression induces angioblast migration and proliferation and stimulates angiogenic remodeling.
        Dev Biol. 2000; 223: 383-398
        • Williams G.A.
        • Eisenstein R.
        • Schumacher B.
        • Hsiao K.C.
        • Grant D.
        Inhibitor of vascular endothelial cell growth in the lens.
        Am J Ophthalmol. 1984; 97: 366-371
        • Rutland C.S.
        • Mitchell C.A.
        • Nasir M.
        • Konerding M.A.
        • Drexler H.C.A.
        Microphthalmia, persistent hyperplastic hyaloid vasculature and lens anomalies following overexpression of VEGF-A188 from the αA-crystallin promoter.
        Mol Vis. 2007; 13: 47-56