Lenticular Neovascularization Subsequent to Traumatic Cataract Formation

Kabat, Alan G.

Optometry & Vision Science:
doi: 10.1097/OPX.0b013e31822311e2
Clinical Report

Purpose. To report a series of cases involving neovascularization within the human crystalline lens—a normally avascular structure—after ocular trauma. This is a retrospective, consecutive observational case series with review of the prevailing literature.

Methods. Four individuals with a history of ocular trauma and subsequent cataract development were examined between May 2004 and April 2007. All had hypermature cataracts and intraocular inflammation, presumably secondary to phacolysis; two of the four had concurrent hyphema and ocular hypertension in the involved eye.

Results. All subjects in this series were found to display a discrete network of blood vessels within the structure of the crystalline lens, just beneath the anterior lens capsule.

Conclusions. Neovascularization of the crystalline lens has received little attention in the ophthalmic literature, having been described only rarely in individual case reports. This manuscript details the first known case series involving lenticular neovascularization, and offers insight into its possible developmental mechanism.

Author Information


Nova Southeastern University, College of Optometry, Fort Lauderdale, Florida.

Received: January 30, 2011; accepted April 19, 2011.

Alan G. Kabat, Nova Southeastern University, College of Optometry, 3200 South University Drive, Fort Lauderdale, Florida 33328, e-mail: kabat@nova.edu

Article Outline

Neovascularization describes a physiological or pathological process whereby proliferation of blood vessels ensues within tissue that does not normally contain such vasculature. Corneal neovascularization is a well-known phenomenon and is seen in numerous conditions that involve hypoxic stress and/or inflammation; etiologic factors may include contact lens abuse, microbial infection, interstitial keratitis, atopic keratoconjunctivitis, or chemical injury.1 The pathogenesis of corneal neovascularization involves development of new vessels from existing capillaries and venules of the pericorneal plexus, which breach the limbal architecture and extend into the corneal periphery. This process and its various manifestations have been extensively documented.2 In contradistinction, however, neovascularization of the crystalline lens is exceedingly rare and has been only scarcely described in the medical literature. Similarly, the pathophysiology of lenticular neovascularization appears to be poorly understood.

A small number of cases have been reported describing intralenticular neovascularization and/or intralenticular hemorrhage associated with ocular trauma.2–5 This manuscript depicts a series of four patients, seen within a primary care optometric clinic, who presented with discrete lenticular neovascularization. All four individuals had a history of antecedent ocular trauma (range, 1 to 44 years) and subsequently developed cataracts, which progressed to hypermaturity. All presented with notable intraocular inflammation, presumably secondary to phacolysis; two of the four had concurrent hyphema and elevated intraocular pressure in the involved eye.

Back to Top | Article Outline


Case 1

A 47-year-old Caribbean Black male presented with diminished vision and severe pain in his left eye. He reported that he had gradually lost vision over several months after being struck in the eye by a tree branch about 1 year earlier; the pain did not ensue until several months later. According to the patient, lack of finances had prevented him from seeking medical attention. Examination revealed corrected visual acuity of 20/60 OD and no light perception in the left eye. A left relative afferent defect was present. Biomicroscopy revealed several corneal scars in both eyes, but no evidence of perforating injury in either eye. A hypermature cataract was immediately evident in the left eye. A mild anterior chamber reaction was noted, with areas of posterior synechiae superiorly. Goldmann applanation tonometry revealed intraocular pressures of 14 mm Hg OD and 12 mm Hg OS. B-scan ultrasonography revealed normal globe contour with no evidence of retinal detachment, masses, or vitreous hemorrhage. Treatment was initiated with scopolamine 0.25% bid OS. At follow-up, the patient reported greatly improved comfort. Reexamination through the now dilated pupil displayed subcapsular intralenticular neovascularization throughout the upper one-third of the crystalline lens (Fig. 1A, B). The patient was ultimately referred for consultation regarding medically necessary cataract extraction, despite evidence to suggest optic nerve damage as indicated by the afferent pupillary defect.

Back to Top | Article Outline
Case 2

A 54-year-old white man presented with acute pain and redness of the right eye since the previous day. He reported a long-standing history of reduced vision in that eye after penetrating ocular trauma 30 years earlier. He claimed to be in good health and reported taking no medications except acetaminophen for the associated pain. Upon examination, best-corrected visual acuity was light perception OD, 20/20 OS. The right pupil was fixed and surgically corectopic. An afferent pupillary defect was present (by reverse testing) in the right eye. Biomicroscopy displayed a profound inflammatory reaction with grade 4 cells and flare in the anterior chamber of the right eye. Evidence of penetrating injury was notable in a linear scar through the inferior cornea and nasal sclera. A dense cataract was present in the right eye with overlying fibrosis and a fine vascular network just beneath the capsule (Fig. 2). A small hyphema was evident at the inferior aspect of the lens. Applanation tonometry revealed intraocular pressure of 18 mm Hg OD and 11 mm Hg OS at 9:40 a.m. The fundus was completely obscured by the cataract, despite pharmacologic dilation in the right eye. The patient was initiated on a regimen of atropine 1% bid and prednisolone acetate 1% hourly, in the right eye. He was promptly referred for surgical consultation regarding cataract extraction, which was successfully performed about 1 month after the initial presentation. After removal of the lens and fibrotic material, an intraocular lens was placed in the posterior chamber; final visual acuity with correction 3 months postoperatively was 20/50.

Back to Top | Article Outline
Case 3

A 63-year-old white man presented for a comprehensive ocular evaluation with a chief complaint of occasional foreign body sensation in his right eye. His ocular history included an automobile accident at the age of 19 years, in which he reportedly damaged his right optic nerve and suffered reduced vision ever since. His medical history was reportedly unremarkable. Upon examination, the right eye was found to have no light perception, whereas the left eye achieved 20/20 with a slight hyperopic correction. The right pupil was irregular and fixed, and displayed a positive afferent defect by reverse testing. Biomicroscopic examination revealed pronounced conjunctival and episcleral injection in the right eye, particularly in the limbal region. Mild (1 to 2 mm) corneal neovascularization was evident, along with substantial iris neovascularization spanning the distance from the pupillary margin to the angle (Fig. 3A). A small inferior hyphema was also present in the right eye, and trace inflammatory cells were noted within the anterior chamber (Fig. 3B). Inspection of the lens revealed a hypermature cataract with an irregular surface and several cystic/calcific inclusions. A well-defined neovascular network was evident along the surface of the lens and extending just beneath the lens capsule. Intraocular pressure as measured via applanation tonometry was 41 mm Hg OD and 22 mm Hg OS. Gonioscopy revealed neovascularization within the angle for about 120° inferiorly in the right eye. Therapy consisting of atropine 1% bid, prednisolone acetate 1% qid, and topical betaxolol 0.25% bid was initiated. The patient was advised to return subsequent to a planned holiday overseas; unfortunately, he did not keep the appointment and was lost to follow-up.

Back to Top | Article Outline
Case 4

A 33-year-old Caribbean Black man presented with a long-standing history of diminished vision in the right eye, associated with ocular trauma during childhood. He complained of moderate, intermittent pain in that eye, occurring about every other day and lasting for 3 to 4 hours. His medical history was reportedly unremarkable; however, he did claim to have seen a doctor in Haiti about 1 year earlier regarding his right eye. According to the patient, topical atropine had been prescribed at that time, but the patient subsequently immigrated to the United States and discontinued therapy. Examination revealed best-corrected acuity of light perception OD and 20/30 OS. Both pupils were irregular in shape and minimally reactive due to posterior synechia; however, a relative afferent pupillary defect was noted in the right eye. Biomicroscopy revealed four clock-hours of peripheral anterior synechia superotemporally OD, along with moderate injection of the conjunctiva and episclera (Fig. 4A). The anterior chamber displayed trace (i.e., <5) inflammatory cells in the right eye. A hypermature cataract was noted in the right eye after pharmacologic dilation. A fine vascular network appeared to emanate inferonasally from areas of posterior iris synechia, extending several millimeters centrally just beneath the anterior lens capsule (Fig. 4B). Intraocular pressure was measured at 20 mm Hg OD and 17 mm Hg OS by applanation tonometry. No view of the fundus was obtainable in the right eye. The patient was started on a regimen of 0.25% scopolamine bid and prednisolone acetate 1% qid, and referred for consultation regarding cataract extraction. Unfortunately, financial constraints prevented him from undergoing the procedure, and he was eventually lost to follow-up.

Back to Top | Article Outline


The most thorough discourse involving lenticular neovascularization to date involves a case presented by Hwang et al.2 in 2002; these authors described a 73-year-old woman with a history of penetrating injury 1 year before presentation. A hypermature cataract was seen in the involved eye, with concurrent posterior iris synechiae. Upon cataract extraction, extensive hemorrhage occurred. Gross evaluation and histological examination of the lens revealed “abundant stromal neovascularization.” The authors provided both a photograph of the lens in vivo and a hematoxylin and eosin stained section of the excised lens, demonstrating the intrinsic vascular network. Subsequent communications in the journal revealed two additional cases of intralenticular hemorrhage associated with ocular trauma, one in a 10-year-old boy and the other in a 25-year-old woman.3,4 Unfortunately, neither of these cases were supported by photographic evidence or histological studies. Several other reports of lenticular hemorrhage are documented in the literature, though none of these are suggestive of a neovascular process.6–9 Rather, the common etiology in these cases appears to be collateral tissue damage associated with incisional cataract or glaucoma surgery or peripheral laser iridotomy.

Interestingly, neovascularization involving the anterior or posterior lens capsule has been reported in pseudophakic patients after cataract extraction.10–12 This phenomenon, while unusual, may be more likely to occur in patients with known vasoproliferative conditions such as severe diabetic retinopathy or ischemic retinal vein occlusion. One of these reports implicated a cyclitic membrane, which may have developed after pars plana vitrectomy and pneumatic retinopexy 2 years before.10

Despite recognition of this unique phenomenon, our understanding of the pathogenesis and even the source of lenticular neovascularization remains speculative. The four cases described herein share common elements with each other and with the seminal case presented by Hwang et al.: all were associated with previous trauma; all displayed some level of intraocular inflammation concurrent with a hypermature cataract; and all had notable areas of posterior synechiae.

It has been proposed that neovascularization results when the normal antiangiogenic mechanisms are disrupted and overcome by pro-angiogenic factors.2,13–15 Numerous conditions can evoke the release of these angiogenic stimuli; among the most common are chronic hypoxia and inflammation.2,15 Recognized ocular angiogenic factors include not only vascular endothelial growth factor (VEGF) primarily, but also basic fibroblast growth factor (bFGF), transforming growth factor beta (TGF-β), and interleukin-8 (IL-8)—all of which are expressed at significantly higher than normal levels during extreme or prolonged inflammation.15–19

It is believed that the lens capsule is responsible in large part for maintaining the antiangiogenic mechanisms of the crystalline lens.2,20 The iris on the other hand is a richly vascularized tissue that is very much prone to neovascularization in cases of ischemic or inflammatory disease. Iris neovascularization (i.e., rubeosis irides) may be observed clinically as the presence of fine arborizations that course over the iris surface in a radial or web-like fashion (Fig. 3B). Iris neovascularization may also be encountered in cases of uveitis.19 Hence, the pathogenesis of lenticular neovascularization in the cases presented might well involve a complex cascade of events, beginning with ocular trauma.

Back to Top | Article Outline
Presumed Pathogenesis of Lenticular Neovascularization

Traumatic ocular injury has the capacity to disrupt the delicate lens fibers, giving rise to rapid onset cataractogenesis (as in case 1), or simply provoking more rapid and severe cataract development over time (cases 2 to 4). As the cataract progresses toward hypermaturity, the lens cortex undergoes spontaneous lysis and absorption; this leads to lens shrinkage and capsular wrinkling, ultimately allowing leakage of high molecular weight lens proteins through the capsule. Because these proteins are antigenic, an immune-mediated inflammatory response may ensue. This process is known as phacolysis.21 The phacolytic response provides an antigenic stimulus which, if not properly addressed, can result in chronic or acute inflammation. Subsequent production of pro-inflammatory, angiogenic mediators stimulates iris neovascularization, and also leads to the development of posterior synechiae Continued lens deterioration may ultimately weaken and/or rupture the lens capsule, providing a point of access for neovascular membranes in adjacent areas of synechiae. This proximity between iris and lenticular neovascularization may or may not be readily visible, depending upon (1) the density and distribution of iris pigment; (2) the location, caliber, and extent of the neovascular iris vessels; or (3) whether the neovascular “feeder vessels” are distributed along the anterior or the posterior surface of the iris. Once the vasculature has gained access to the lens, further proliferation within the matrix is potentiated by inflammatory down-regulation of anti-angiogenic compounds, and a network of vessels may be observed within the crystalline lens.2,4

Back to Top | Article Outline

Only one of the cases presented herein is known to have received definitive treatment. Cases 1, 3, and 4 were ultimately lost to follow-up, as is often the case in socioeconomically challenged patients. The individual in case 2 underwent successful extracapsular cataract extraction and regained functional vision in the involved eye. Historically, there have been only two recognized solutions for patients with phacolysis. The first and most common treatment option is to perform surgical lensectomy.21,22 The other strategy is aimed at maintaining adequate intraocular pressure through medical therapy while awaiting spontaneously lens absorption.23 Management of chronic ocular ischemia is somewhat more challenging. Traditional therapy to treat ocular neovascularization has generally consisted of pan-retinal laser photocoagulation, which induces selective destruction of retinal capillary beds for the purpose of reducing oxygen demand, thereby decreasing the release of vasoproliferative substances.24–27 However, this technique relies on a clear ocular media, and in the case of hypermature cataract pan-retinal laser photocoagulation is simply not a feasible option.

The newest modality to treat both anterior and posterior ocular neovascularization is the family of pharmaceutical VEGF inhibitors, examples of which include ranibizumab and bevacizumab. VEGF normally interacts with receptors on the surface of endothelial cells, promoting angiogenesis in vessel-rich tissues such as the uvea. Anti-VEGF agents bind to and inhibit the biological activity of VEGF, preventing it from reaching those receptors and preventing microvascular growth.28 In recent years, anti-VEGF therapies have been used successfully in the treatment of numerous conditions involving anterior segment angiogenesis, particularly neovascular glaucoma.29–32 Additionally, VEGF inhibitors have been used in the treatment of corneal neovascularization associated with a variety of disorders, including trauma, Stevens-Johnson syndrome, limbal stem cell deficiency, postinfectious keratitis, ocular cicatricial pemphigoid, interstitial keratitis, Terrien's marginal degeneration, sclerokeratitis, stromal herpetic keratitis, and iatrogenic disease after penetrating keratoplasty.33–38 Because the cornea is similar to the lens in that it enjoys angiogenic privilege, it is conceivable that anti-VEGF therapies might prove beneficial for lenticular neovascularization.39 To date, no such cases have been published, although a singular case of posterior capsule neovascularization associated with capsular opacification after uncomplicated cataract surgery was reported in 2007.40 That patient was successfully treated with intravitreal injection of 1.25 mg bevacizumab, which induced complete regression of the vessels after 1 week, allowing for definitive treatment with Nd:YAG posterior capsulotomy.10

Back to Top | Article Outline


Although several case reports of lenticular neovascularization have been published, little research has been directed to this curious and rare phenomenon. The series presented herein describes four cases of lenticular neovascularization encountered in a primary eye care setting over 3 years time; moreover, it delineates the specific conditions and circumstances that may indeed be crucial in the pathogenesis of this unique entity. These include antecedent ocular trauma, phacolysis, uveitic inflammation, posterior synechia formation, and rubeosis irides. Although others have proposed that penetrating ocular trauma is necessary for lenticular neovascularization to develop,4 the cases described in this series suggest otherwise. Anti-VEGF therapies may hold promise for future treatment of this rare but sight-threatening ocular condition.

Alan G. Kabat

Nova Southeastern University

College of Optometry, 3200 South University Drive

Fort Lauderdale, Florida 33328

e-mail: kabat@nova.edu

Back to Top | Article Outline


1.Chang JH, Gabison EE, Kato T, Azar DT. Corneal neovascularization. Curr Opin Ophthalmol 2001;12:242–9.
2.Hwang YS, Lai CC, Lee JS, Yang KJ, Chen TL. Posttraumatic neovascularization in a cataractous crystalline lens. J Cataract Refract Surg 2002;28:715–6.
3.Pangtey MS, Khokhar S, Sony P, Panda A, Sethi HS, Chandra P. Posttraumatic neovascularization in a cataractous crystalline lens. J Cataract Refract Surg 2003;29:859–60.
4.Natarajan R, Rao SK. Posttraumatic neovascularization. J Cataract Refract Surg 2003;29:861.
5.Rao SN, Smith RE. Intralenticular hemorrhage following blunt ocular trauma. Arch Ophthalmol 1998;116:1258–9.
6.Feibel RM, Bigger JF, Smith ME. Intralenticular hemorrhage following iridectomy. Arch Ophthalmol 1972;87:36–8.
7.Ferry AP. Hemorrhage into the lens as a complication of glaucoma surgery. Am J Ophthalmol 1976;81:351–4.
8.Montgomery DM, Dutton GN. Intralenticular haemorrhage complicating pulsed laser iridotomy. Br J Ophthalmol 1987;71:484.
9.Barker NH, Callender D. Intralenticular haemorrhage complicating trabeculectomy. Eye (Lond) 1995;9(Pt 3):383–4.
10.Eren E, Küçükerdönmez C, Yilmaz G, Akova YA. Regression of neovascular posterior capsule vessels by intravitreal bevacizumab. J Cataract Refract Surg 2007;33:1113–5.
11.Ulbig MR, Hykin PG, Foss AJ, Schwartz SD, Hamilton PA. Anterior hyaloidal fibrovascular proliferation after extracapsular cataract extraction in diabetic eyes. Am J Ophthalmol 1993;115:321–6.
12.Lewis H, Abrams GW, Williams GA. Anterior hyaloidal fibrovascular proliferation after diabetic vitrectomy. Am J Ophthalmol 1987;104:607–13.
13.Casey R, Li WW. Factors controlling ocular angiogenesis. Am J Ophthalmol 1997;124:521–9.
14.Aiello LP, Northrup JM, Keyt BA, Takagi H, Iwamoto MA. Hypoxic regulation of vascular endothelial growth factor in retinal cells. Arch Ophthalmol 1995;113:1538–44.
15.Kvanta A. Ocular angiogenesis: the role of growth factors. Acta Ophthalmol Scand 2006;84:282–8.
16.Friedlander M. Fibrosis and diseases of the eye. J Clin Invest 2007;117:576–86.
17.Zhang SX, Ma JX. Ocular neovascularization: implication of endogenous angiogenic inhibitors and potential therapy. Prog Retin Eye Res 2007;26:1–37.
18.Dorrell M, Uusitalo-Jarvinen H, Aguilar E, Friedlander M. Ocular neovascularization: basic mechanisms and therapeutic advances. Surv Ophthalmol 52(suppl. 1):S3–19, 2007.
19.Kuo IC, Cunningham ET, Jr. Ocular neovascularization in patients with uveitis. Int Ophthalmol Clin 2000;40:111–26.
20.Sasaki T, Larsson H, Tisi D, Claesson-Welsh L, Hohenester E, Timpl R. Endostatins derived from collagens XV and XVIII differ in structural and binding properties, tissue distribution and anti-angiogenic activity. J Mol Biol 2000;301:1179–90.
21.Sowka J, Vollmer L, Falco L. Rapid onset phacolysis. Optometry 2004;75:571–6.
22.Braganza A, Thomas R, George T, Mermoud A. Management of phacolytic glaucoma: experience of 135 cases. Indian J Ophthalmol 1998;46:139–43.
23.Mohan M, Bartholomew RS. Spontaneous absorption of a cataractous lens. Acta Ophthalmol Scand 1999;77:476–7.
24.Little HL, Rosenthal AR, Dellaporta A, Jacobson DR. The effect of pan-retinal photo-coagulation on rubeosis iridis. Am J Ophthalmol 1976;81:804–9.
25.Jacobson DR, Murphy RP, Rosenthal AR. The treatment of angle neovascularization with panretinal photocoagulation. Ophthalmology 1979;86:1270–7.
26.Flanagan DW, Blach RK. Place of panretinal photocoagulation and trabeculectomy in the management of neovascular glaucoma. Br J Ophthalmol 1983;67:526–8.
27.Wolbarsht ML, Landers MB, III. The rationale of photocoagulation therapy for proliferative diabetic retinopathy: a review and a model. Ophthalmic Surg 1980;11:235–45.
28.Kaiser PK. Antivascular endothelial growth factor agents and their development: therapeutic implications in ocular diseases. Am J Ophthalmol 2006;142:660–8.
29.Kahook MY, Schuman JS, Noecker RJ. Intravitreal bevacizumab in a patient with neovascular glaucoma. Ophthalmic Surg Lasers Imaging 2006;37:144–6.
30.Silva Paula J, Jorge R, Alves Costa R, Rodrigues Mde L, Scott IU. Short-term results of intravitreal bevacizumab (Avastin) on anterior segment neovascularization in neovascular glaucoma. Acta Ophthalmol Scand 2006;84:556–7.
31.Iliev ME, Domig D, Wolf-Schnurrbursch U, Wolf S, Sarra GM. Intravitreal bevacizumab (Avastin) in the treatment of neovascular glaucoma. Am J Ophthalmol 2006;142:1054–6.
32.Yazdani S, Hendi K, Pakravan M. Intravitreal bevacizumab (Avastin) injection for neovascular glaucoma. J Glaucoma 2007;16:437–9.
33.Yoeruek E, Ziemssen F, Henke-Fahle S, Tatar O, Tura A, Grisanti S, Bartz-Schmidt KU, Szurman P. Safety, penetration and efficacy of topically applied bevacizumab: evaluation of eyedrops in corneal neovascularization after chemical burn. Tübingen Bevacizumab Study Group. Acta Ophthalmol 2008;86:322–8.
34.Bahar I, Kaiserman I, McAllum P, Rootman D, Slomovic A. Subconjunctival bevacizumab injection for corneal neovascularization. Cornea 2008;27:142–7.
35.Qian CX, Bahar I, Levinger E, Rootman D. Combined use of superficial keratectomy and subconjunctival bevacizumab injection for corneal neovascularization. Cornea 2008;27:1090–2.
36.Doctor PP, Bhat PV, Foster CS. Subconjunctival bevacizumab for corneal neovascularization. Cornea 2008;27:992–5.
37.Uy HS, Chan PS, Ang RE. Topical bevacizumab and ocular surface neovascularization in patients with stevens-johnson syndrome. Cornea 2008;27:70–3.
38.Bock F, Konig Y, Kruse F, Baier M, Cursiefen C. Bevacizumab (Avastin) eye drops inhibit corneal neovascularization. Graefes Arch Clin Exp Ophthalmol 2008;246:281–4.
39.Cursiefen C. Immune privilege and angiogenic privilege of the cornea. Chem Immunol Allergy 2007;92:50–7.

angiogenesis; crystalline lens; intralenticular; hypermature cataract; neovascularization; ocular trauma; phacolysis; rubeosis irides; synechia; uveitis; VEGF

© 2011 American Academy of Optometry