Prevalence of Primary Angle Closure in Retinal Vein Occlusion

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Ralf Francis
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This paper was conferred with the AIOS D.B. CHANDRA DISHA AWARD for the BEST FREE PAPER of Glaucoma Sessions. Also judge the Best Free Paper of Glaucoma-II Session. DR. MADHU BHOOT: M.B.B.S. (2003), V.

(2009), JPM Rotary Eye Hospital & Research Institute, Orissa; Fellowship in Medical Retina (2011); Fellowship in IOL and Microsurgery (2014); Fellowship in Glaucoma & Anterior Segment (2015).

Madhu Bhoot, Dr. Julie Pegu, Dr. Dubey Suneeta, Dr.

1 This paper was conferred with the AIOS D.B. CHANDRA DISHA AWARD for the BEST FREE PAPER of Glaucoma Sessions. Also judge the Best Free Paper of Glaucoma-II Session. DR. MADHU BHOOT: M.B.B.S. (2003), V.S.S Medical College, Orissa; D.N.B. (2009), JPM Rotary Eye Hospital & Research Institute, Orissa; Fellowship in Medical Retina (2011); Fellowship in IOL and Microsurgery (2014); Fellowship in Glaucoma & Anterior Segment (2015). Presently, Consultant in Glaucoma & Anterior segment at Dr. Shroff s Charity Eye Hospital, New Delhi. drmadhubhoot@gmail.com Prevalence of Primary Angle Closure in Retinal Vein Occlusion Dr. Madhu Bhoot, Dr. Julie Pegu, Dr. Dubey Suneeta, Dr. Manisha Agarwal Glaucoma is considered as the leading cause of irreversible blindness worldwide, with Asians accounting for approximately half of the world s glaucoma cases. 1 It also has been accepted that primary angle closure glaucoma (PACG) is higher in Asians than Europeans and Africans, with over 80% of those with PACG in Asia. 1,3 Because PACG appears to cause blindness more frequently than primary open angle glaucoma (POAG), it is an important public health issue. Retinal vascular obstructive disease is one of the commonest vascular diseases of eyes, second only to diabetic retinopathy. 24 In the population-based Blue Mountains Eye Study, the prevalence of retinal vein occlusion was 1.6%. 4 Data from previous studies have shown an association of retinal branch vein occlusion with hypertension, athero-sclerotic vascular disease, diabetes mellitus, rheological factors, refractive error, elevated intraocular pressure, and openangle glaucoma, although these associations have not been consistent A less well recognized association between angle-closure glaucoma and retinal vein occlusion (RVO), has been reported in a small number of cases in older articles. 20,21 The incidence of primary open angle glaucoma in patients with central vein occlusion has been reported to be 5.7% to 65.5% 22,23 and with branch retinal vein occlusion to be 6.6% to 15%. The incidence of primary angle closure glaucoma in association with central retinal vein occlusion (CRVO) is generally reported to be 0 to and 1.72% in cases of branch retinal vein occlusion (BRVO). 20 This clearly leaves much uncertainty regarding any described association. Furthermore, since the first reports of angle-closure and RVO, 20,21 there have been limited additional data. To date there has only been one case series showing association between primary angle closure (PAC) and RVO. 12 Identification and reporting of such a link between RVO and angle closure is also significant as patients with RVO will undergo regular pupillary dilation during hospital follow-up visits. Probably even more important is the fact that it is an eminently treatable

2 Other Best Free Papers risk factor. Secondly, the direction of the association is not clear. Verhoeff 25 postulated that probably the increased IOP compresses and collapses the wall of the central retinal vein (CRV), leading to intimal proliferation in the vein, which he had found in his histo-pathologic studies to be the primary cause of CRVO. 26 Similarly, Salzmann 27 thought that glaucoma might lead to venous occlusion by causing collapse of the veins. Duke-Elder and Dobree 28 stated that the incidence of thrombosis shows little dependence on the height of IOP, and that it would seem probable that the association is due to the venous stasis induced by the raised IOP; the frequent presence of arterial disease in these cases might also be an etiologic factor. Vannas and Tarkkanen in their study felt primary glaucoma to be a bad prognostic factor in cases of venous occlusion. 20 Central retinal vein occlusion (CRVO) has also been reported to cause shallowing of the anterior chamber leading to acute angle closure glaucoma. 11,29 This is due to anterior displacement of the lens-iris diaphragm caused by either the transudation of fluid from retinal vessels into the vitreous cavity or swelling of the ciliary body due to spasm, oedema, or detachment which may cause relaxation of lens zonules with subsequent crowding and closure of the angle. 29,30 The question we are looking an answer for Is there a role of angle closure in the development of RVO. As there has been no prospective study till date to answer this question this study was undertaken to determine the prevalence of primary angle closure in patients with RVO reporting to a tertiary eye care centre in Northern India. MATERIALS AND METHODS This was a prospective, observational, cross-sectional study conducted at a tertiary eye care institute which included all patients diagnosed with RVO between May 2013 and April This study was approved by the Hospital Institutional Review Board. All patients diagnosed as RVO were considered for glaucoma evaluation. Inclusion criteria All cases of retinal vein occlusion were included in the study. Exclusion criteria a. Any media opacity precluding view of retina (Dense corneal opacity, Dense cataract) b. Retinal vein occlusion with associated neovascularisation of iris/angle c. Pseudophakia in the involved eye. Informed consent was taken from each patient. A detailed medical and surgical history was taken. Past medical history about Hypertension, Diabetes Mellitus and Coronary Artery Disease and

3 Hyperlipidemia was noted. Clinical examination included Snellen s visual acuity, slit lamp biomicroscopy (including Van Herick s grading and lens status), Goldmann applanation tonometry (average of three readings), gonioscopy, fundus examination under full mydriasis by retina specialist, optic nerve head evaluation(onh) under full mydriasis by a glaucoma specialist and ultrasound A-scan biometry. Gonioscopy was performed in all cases by a single examiner (JP) using a Posner s 4-mirror indirect gonioscopy lens in dim illumination using a shortened slit beam that did not fall upon the pupil. The gonioscopic finding was rechecked by another masked glaucoma specialist (SD) using the same lens. Grading of the irido-corneal angle was done according to the Spaeth s classification. Detailed fundus evaluation was done by indirect ophthalmoscopy with a Volk 20 D lens and at the slit lamp with a Volk 90 D lens for ONH evaluation. Mydriatic (Tropicamide 1%) drops were used to dilate the pupil. A-scan ultrasonography using the Ocuscan Rxp machine was performed for each patient to measure anterior chamber depth (ACD) in both eyes to determine shallow anterior chamber (AC). Biometry was performed by an optometrist after anterior segment examination and gonioscopy was completed by an ophthalmologist. Biometry was performed in all subjects before the use of any mydriatic agent. Diagnostic criteria for CRVO, BRVO, and HRVO are provided in Table -1 Classification of primary angle closure (PAC): PACS or Occludable Angle - An eye where less than180 degrees of the filtering trabecular meshwork was visible before indentation. PAC - An eye with an occludable drainage angle and features indicating that trabecular obstruction by the peripheral iris has occurred, such as peripheral anterior synechiae (PAS), iris whorling (distortion of the radially orientated iris fibres), glaucomflecken lens opacities, or excessive pigment deposition on the trabecular surface without disc or visual field changes PACG PAC with intraocular pressure more than 21 mm Hg. Visual field and optic disc changes were not mandatory for the diagnosis of PACG because of decrease in visual acuity and obliteration of ONH view in many patients due to the venous occlusion. However, in cases where the ONH was not involved, glaucomatous changes were noted and included in the diagnosis of PACG. RESULTS 60 subjects were included in the study, comprising 29 males and 31 females with an average age of 58.3 years (range 28 to 59 years). Out of total 60 patients of RVO, 27 patients (45%) had CRVO and 33 patients (55%) had

4 Other Best Free Papers BRVO (Table 2). Ratio of BRVO with CRVO was In patients who had sustained a BRVO, open angles was seen in 15 patients (45%), Primary Open Angle Glaucoma (POAG) in 6 patients (18%), PACS in 1 patient (3%), PAC in 4 patients (12%) and PACG in 7 patients (21%). In those with CRVO, open angles was seen in 9 patients (33%), POAG in 3 patients (11%), PACS in 3 patients (11%), PAC in 3 patients (11%) and PACG in 9 patients (33%) (Table 4). In the contra-lateral normal eyes of patients with BRVO, open angles were seen in 16 patients (48%), OAG, PAC, PACS in 5 patients each (15%) and PACS in 2 patients (6%) whereas in the contra-lateral eye of patients with CRVO, open angles were seen in 11 patients (41%), OAG in 2 patients (7%), PACS in 3 patients (11%), PAC in 4 patients (15%) and PACG in 7 patients (26%). Chi-square test was used to compare the risk of PAC between the two groups, CRVO and BRVO. There was no significant difference (p = 0.09) in the risk of PAC in eyes with either CRVO or BRVO. Presenting IOP ranged from 10 to 46 mmhg. ACD was < 3mm in 9 patients (69%) of CRVO with PAC and in 7 patients (70%) of BRVO with PAC (Table 6). This showed significant correlation between ACD measured by A-scan biometry and gonioscopic grading. Mean ACD was 2.96 mm in patients with PAC with a Standard Deviation (SD) of ± Mean axial length was mm in patients with PAC with a SD of ± 3.40 in the diseased eye. A significant proportion of subjects in this series (65%) had a past history of hypertension. 22 patients (67%) of BRVO had HTN, 5 patients had co-existing DM and CAD whereas 6 patients had no known systemic risk factor. 12 patients (44%) of CRVO had HTN, 3 patients has co-existing DM and CAD whereas 12 patients had no known systemic risk factor. In patients with no systemic association, in the eyes sustaining BRVO, four out of six patients had PACG and one had POAG. In the CRVO group, three out of 12 patients had PACG, one had POAG, one had PACS and one had PAC. The rest of the Table 1: Diagnostic Criteria Central retinal vein occlusion: Flame-shaped, dot or punctate retinal hemorrhages or both in all four quadrants of the retina, dilation and increased tortuosity of the retinal veins, and optic disc swelling. Branch retinal vein occlusion: Initially: Either flame-shaped, dot or punctuate retinal hemorrhages in the distribution of the occluded branch retinal vein with the apex of the obstructed tributary system located at an arteriovenous crossing. Later: Criteria expanded to include cases in which retinal hemorrhages had resolved and new vessels or collateral vessels had developed. Hemiretinal vein occlusion: Same as for branch retinal vein occlusion but involving the superior or inferior half of the retina.

5 Table 2 RVO Total Percentage CRVO BRVO Table 3 PAC CRVO Percentage BRVO Percentage Total Percentage Present Absent Total Table 4: Diseased Eye Gonioscopy BRVO % CRVO % Total Open angles OAG PACS PAC PACG Total Table 5: Normal Eye Gonioscopy Contra-lateral % Contra-lateral % Total Eye (BRVO) Eye (CRVO) Open Angles OAG PACS PAC PACG Total Table 6 BRVO (%) CRVO (%) Total ACD PAC Open PAC Open > patients had open angles. 2 patients of PACG with CRVO and 1 patient of PACG with BRVO had higher IOP in the diseased eye.

6 Other Best Free Papers All patients with narrow angles underwent peripheral laser iridotomies following which widening of the drainage angle was noted except in the areas of PAS. DISCUSSION The prevalence of angle closure shows much wider variations than for open angle glaucoma. 2 To date there is limited data on the association between PAC and RVO. Recently there has been only one retrospective case series where 19 subjects were studied who had sustained an RVO and had PAC. They found that majority of patients were diagnosed with PACG in one or both eyes suggesting that PAC leads to RVO, rather than the reverse association. To the best of our knowledge, this is the first prospective case study to assess the prevalence of PAC in patients with RVO ascertained over a 1 year period. Among primary glaucoma, POAG in particular seems to have a close association with RVO as seen in older literature. Articles concerning occlusion of the central retinal vein have occasionally made allusions to the depth of the anterior chamber, without apparently attaching particular significance to it. In our study we have seen that mean ACD was 2.96 mm in eyes with RVO and PAC whereas, mean ACD was 2.99 mm in the contralateral eye which had PAC with RVO. Identifying these patients is important because these patients will require frequent pupillary dilatation on follow up visits which might precipitate an angle closure attack. Moreover several treatment options are available to improve the drainage angle configuration and thus prevent angle closure episodes. Similar results have been seen in a study done by R George et. al. 13 where they compared ocular biometric values in a population based sample of eyes with occludable angles, angle closure glaucoma, and normal subjects and found that eyes with angle closure glaucoma or occludable angles have shorter axial lengths, shallower anterior chamber depths, and thicker crystalline lenses. Increasing age is a risk factor for angle closure. Also majority of the patients in this study were in the age group of 60 to 89 years. Mean age of the patients was 58.3 years. This gives the impression that middle and elderly age group are at risk which was also seen in the study by R George et. al. 13 They found the mean age among subjects with occludable angles was years (95% CI: to 55.96), significantly higher (p<0.001) than the years (95% CI: to 50.90) among normal subjects. It is known that women are more susceptible to angle closure glaucoma than men. 13,14 We also found a significantly larger proportion of women in the group with occludable angles, 31 patients (52%) being females and 29 patients (48%), males. PACG was seen in 33% of cases with CRVO whereas it was seen in 21% cases of BRVO. Vannas and Tarkkanen in their study found the prevalence of PACG to be 5.6% in CRVO and 1.7% in BRVO. On comparing the diseased

7 eye and the normal eye in our study, it was seen that glaucoma was also present in the normal eye in majority of the patients who had glaucomatous changes in the eyes with RVO. Thus the cause for narrow angles in patients with angle closure and RVO is probably pupillary block and not anterior displacement of the lens-iris diaphragm caused by either the transudation of fluid from retinal vessels into the vitreous cavity or swelling of the ciliary body due to spasm, oedema, or detachment which may cause relaxation of lens zonules with subsequent crowding and closure of the angle 29,30 as mentioned by Phelps and Grants in their study. The pupillary block mechanism is also supported by the fact that the angle configuration had improved after YAG PI except in the areas of PAS formation. Hypertension was found to be the major systemic risk factor in patients with RVO in our study. In Beaver Dam, strong associations of hypertension, focal arteriolar narrowing, and arteriovenous nicking with prevalent retinal branch vein occlusion was seen whereas in the Blue Mountains population, 4 branch vein occlusion was associated with stroke and angina but not myocardial infarction. In the Eye Disease Case Control Study8, in addition to hypertension, it was associated with a history of cardiovascular disease and with increased body mass index. Most of the patients in our series had angle closure glaucoma in both eyes suggesting that PAC may lead to RVO especially in patients with systemic risk factors like HTN. However, it has also been seen in our study that in patients with no systemic association, the eye with higher IOP sustained venous occlusion suggesting that increased IOP could be an independent risk factor leading to RVO which was also seen by Verhoeff, 25 Salzmann, 26 Vannas and Orma and Bertelson in their studies. CONCLUSION The association between PAC and RVO is less known. Our study shows that primary angle closure can be an independent risk factor for development of RVO and should be borne in mind while evaluating patients with RVO. Gonioscopy should be done in all patients with RVO at presentation. However, data from larger populations are needed to further assess association between PAC and RVO. REFERENCES 1. Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and Br J Ophthalmol 2006;90: George R, Ve RS, Vijaya L. Glaucoma in India: Estimated burden of disease. J Glaucoma. 2010;19: Wong TY, Loon SC, Saw SM. The epidemiology of age related eye diseases in Asia. Br J Ophthalmol 2006;90:

8 Other Best Free Papers 4. Mitchell P, Smith W, Chang A. Prevalence and associations of retinal vein occlusion in Australia. The Blue Mountains Eye Study. Arch Ophthalmol 1996;114: Glacet-Bernard A, Coscas G, Chabanel A, et. al. Prognostic factors for retinal vein occlusion: A prospective study of 175 cases. Ophthalmology 1996;103: Peduzzi M, Debbia A, Guerrieri F, et. al. Abnormal blood rheology in retinal vein occlusion. Graefes Arch Ophthalmol 1986; McGrath MA, XVechsler F, Hunvor ABL, et. al. Systemic factors contributory to retinal vein occlusion. Arch Interni Med. 1978;138: Anonymous. Risk factors for branch retinal vein occlusion. The Eye Disease Case-Control Study. Am J Ophthalmtol 1993;116: Johnston RL, Brucker AJ, Steinmann XN7, et. al. Risk factors of branch retinal vein occlusion. Arch Ophthalmol. 1985;103: Rath EZ, Frank RN, Shin DH, et. al. Risk factors for retinal vein occlusions: A case-control study. Ophthalmology 1992;99: Sperduto RD, Hiller R, Chew E, et. al. Risk factors for hemiretinal vein occlusion: Comparison writh risk factors for central and branch retinal vein occlusion. The Eye Disease Case-Control Study. Ophthalmology 1998;105: Michaelides M1, Foster PJ. Retinal vein occlusion and angle closure: a retrospective case series. J Glaucoma. 2010;19: R George, P G Paul, M Baskaran, S Ve Ramesh, P Raju, H Arvind, C McCarty, L Vijaya. Ocular biometry in occludable angles and angle closure glaucoma: a population based survey. Br J Ophthalmol 2003;87: Ritch R, Shields B, Krupin T. The glaucomas. 2nd ed. Vol 2. St Louis:Mosby, Hitchings RA, Spaeth GL. Chronic retinal vein occlusion in glaucoma. Br J Ophthalmol. 1976;60: Hayreh SS. Prevalent misconceptions about acute retinal vascular occlusive disorders. Prog Retin Eye Res. 2005;24: Hayreh SS, Zimmerman MB, Beri M, et. al. Intraocular pressure abnormalities associated with central and hemicentral retinal vein occlusion. Ophthalmology. 2004;111: Hirota A, Mishima HK, Kiuchi Y. Incidence of retinal vein occlusion at the Glaucoma Clinic of Hiroshima University. Ophthalmologica. 1997;211: Vannas S: Glaucoma due to thrombosis of the central vein of the retina. Ophthalmologica 142: Vannas S, Tarkkanen A. Retinal vein occlusion and glaucoma. Tonographic study of the incidence of glaucoma and of its prognostic significance. Br J Ophthalmol. 1960;44: Posner A. Central retinal vein thrombosis in angle closure glaucoma. Eye Ear Nose Throat Mon. 1958;37: Waubke T: Glaukomdeposition und Sekundarglaukom bei Tarombosen der Retinagefasse. Klin Monatsbl Augenheilkd 136:

9 23. Dryden RM: Central retinal vein occlusions and chronic simple glaucoma. Arch Ophthalmol 73: Cugati S, Wang JJ, Rochtchina E, Mitchell P. Ten-year incidence of retinal vein occlusion in an older population: the Blue Mountains Eye Study. Arch Ophthalmol 2006;124: Verhoeff FH. The effect of chronic glaucoma on the central retinal vessels. Arch Ophthalmol. 1913;42: Verhoeff FH. Obstruction of the central retinal vein. Arch Ophthalmol 1907;36: Salzmann M. Glaukom und Netzhautzirkulation. In: Streiff EB, ed. Bibliotheca Ophthalmologica. Vol. 15. Berlin: Karger; Duke-Elder S, Dobree JH. Diseases of the Retina, Vol. X. In: Duke-Elder S, ed. System of Ophthalmology. London: Kimpton; 1967; Phelps Cd. Angle-Closure Glaucoma Secondary To Ciliary Body Swelling. Arch Ophthalmol 1974;92: Grant W. Shallowing of the anterior chamber following occlusion of the central retinal vein. Am J Ophthalmol 1973;75:384 9.

STUDY OF EFFECTIVENESS OF LENS EXTRACTION AND PCIOL IMPLANTATION IN PRIMARY ANGLE CLOSURE GLAUCOMA Sudhakar Rao P 1, K. Revathy 2, T.

STUDY OF EFFECTIVENESS OF LENS EXTRACTION AND PCIOL IMPLANTATION IN PRIMARY ANGLE CLOSURE GLAUCOMA Sudhakar Rao P 1, K. Revathy 2, T. Sreevathsala 3 HOW TO CITE THIS ARTICLE: Sudhakar Rao P, K. Revathy,