Visual improvement following glaucoma surgery: a case report
© Foulsham et al.; licensee BioMed Central. 2014
Received: 31 July 2014
Accepted: 19 December 2014
Published: 23 December 2014
Glaucoma is a progressive optic neuropathy and a leading cause of blindness. Neural losses from glaucoma are irreversible, and so the aim of glaucoma treatment is to slow progression and minimize the risk of further damage. Functional improvement with treatment is not expected. We report the case of a patient who experienced a significant improvement in vision following glaucoma surgery and review the literature regarding this phenomenon.
A 64-year old male presented with a 13-month history of gradual vision loss in the right eye to the extent that he could only perceive hand movements. His intraocular pressure (IOP) measured 50 mmHg and he was found to have advanced primary open angle glaucoma. Medical treatment was commenced and he underwent a successful right Mitomycin C-augmented trabeculectomy. Unexpectedly he experienced marked improvement in vision post-operatively, with improvements maintained through six months of follow-up. At his most recent visit visual acuity was 6/18 in the affected eye. Although the mechanism of improved vision cannot be proven it is likely that successful lowering of IOP resulted in some reversal of retinal ganglion cell dysfunction. Important factors may have included his relatively young age, high IOP and short duration of symptoms.
Although rare, functional improvements may occur following trabeculectomy. Glaucoma surgery should be offered early to those with advanced disease, and considered even in those with reduced visual acuity.
KeywordsGlaucoma Trabeculectomy Neuroregeneration
Glaucoma is characterized by progressive optic nerve degeneration, evident clinically as structural changes to the optic nerve head and corresponding loss of visual field . The pathogenesis is not fully understood but it is thought to involve a heterogeneous group of pathological processes that share the final common pathway of progressive death of retinal ganglion cells and their axons . Glaucomatous damage is deemed irreversible; therefore the optimal management currently depends on early detection and treatment to minimize the risk of progression and development of visual loss.
The first line treatment for glaucoma has traditionally consisted of medical management with topical intraocular pressure lowering agents. However, recent guidance, such as that from the United Kingdom National Institute of Clinical Excellence (NICE) stipulate that, for patients with advanced disease at presentation, surgery may be an appropriate first line therapy . The aim of early surgery is to reduce the risk of further deterioration in visual function, as improvement in vision following glaucoma surgery is not expected. There is however, some evidence that retinal ganglion cells damaged by glaucoma might undergo a period of reversible dysfunction preceding cell death [4, 5]. Furthermore, reversible changes in optic nerve head morphology have been reported following reductions of intraocular pressure [6–9]. These observations suggest that certain structural and functional improvements may in fact be possible in some patients.
The aim of the current article is to 1) report the case of a patient with advanced glaucoma at initial presentation that demonstrated marked improvement in visual acuity following reduction in intraocular pressure with trabeculectomy, and 2) to critically appraise the published literature as to whether functional improvement is possible following glaucoma surgery.
The patient described in this case had severe glaucomatous damage at presentation, evident from the marked loss of neural tissue seen on optic disc examination, the presence of extreme thinning of RNFL on OCT, and the severe functional deficit, with a visual acuity of only hand movements and a relative afferent pupillary defect. Such severe disease at presentation conveys a poor prognosis and requires a low target pressure to minimize the risk of visual loss. Surgery was offered with the sole aim of preventing loss of remaining vision and with no expectation for visual recovery. Surprisingly, lowering of IOP resulted in a dramatic improvement in visual function.
Improvements in structural measurements are widely appreciated to occur following successful reduction in intraocular pressure with glaucoma surgery. For example, Kotecha and colleagues have shown using confocal scanning laser ophthalmoscopy that reversal in disc cupping can occur following trabeculectomy . In a series of 22 eyes from 20 patients evaluated using spectral domain OCT, Russo and colleagues have demonstrated significant decreases in cup depth following trabeculectomy at both 1 week and 1 month postoperatively . Increases in RNFL thickness measurements are less widely reported. However, in a small series of 38 eyes of 31 patients with glaucoma, Aydin and colleagues found a significant increase in circumpapillary RNFL thickness following glaucoma surgery. 31 of 38 eyes had an increase in RNFL thickness at 6 to 12 months following surgery, with a mean increase of 12.6 μm . In fact there is a considerable body of evidence demonstrating reversal of structural glaucomatous damage following pressure-lowering surgical interventions, with apparent reversal of structural changes especially common in younger patients with congenital, infantile and juvenile-onset glaucoma [13–17].
In contrast to the improvements observed in structural measurements, evidence for functional improvement following glaucoma surgery is scarce. Leung and colleagues described a single case of a patient with juvenile open-angle glaucoma who recovered from an inferotemporal visual field defect following trabeculectomy . However, due to the variability inherent in visual field testing detecting genuine improvement may be challenging.
Clinical interventions in glaucoma are generally judged on their capacity to reduce the incidence of progression of visual field endpoints, however, few studies have investigated whether improvements in visual function might occur. One exception was the Otago Glaucoma Surgery Outcome Study, which was a prospective case series including 841 eyes of 607 patients with primary open or closed angle glaucoma. Patients were treated with trabeculectomy and followed for an average of 7.5 years. Visual acuity was tested at each visit and categorised as ≥6/9, <6/9 but >6/120, or ≥6/120, with improvement in visual acuity defined by an improvement in class. The results demonstrated 151 of 841 eyes (18%) had an improvement in vision following trabeculectomy . However, a limitation of this study was that 23% of eyes with improvement in vision underwent concurrent cataract extraction. In future surgical glaucoma studies it would be interesting to determine the true incidence of visual improvement.
It is important to consider the possible mechanism of visual improvement in our patient. Although the defining histological feature of glaucoma is loss of retinal ganglion cells and their axons, the exact mechanism of retinal ganglion cell death is not known. Retinal ganglion cell death is believed to be biphasic; with a primary insult initiating damage that provokes a cascade of events, in turn creating a noxious environment that envelops retinal ganglion cells, resulting in secondary cell degeneration . Increased IOP and vascular deregulation may contribute to the primary insult, obstructing axoplasmic flow and altering microcirculation in the optic nerve. The secondary cascade is likely to involve excitotoxic damage from the accumulation of glutamate, increased intracellular calcium and resultant retinal ganglion cell apoptosis .
Once apoptosis has occurred it is difficult to conceive how visual function might improve, however, Swanson and colleagues have proposed that retinal ganglion cells might undergo a period of reversible dysfunction preceding apoptosis . Evidence for this theory largely comes from primate studies of experimental glaucoma. In one study involving rhesus monkeys with unilateral laser-induced experimental glaucoma, Harwerth and colleagues found reductions in visual field sensitivity could be present without apparent retinal ganglion cell loss on histology [23, 24]. Marx and colleagues examined flash and pattern electroretinograms (PERG) in experimental glaucoma [25, 26]. The results showed that 50% reductions in PERG amplitude could occur in the absence of observable glaucomatous optic disc changes. A limitation of these studies is that they utilized animal models of experimental glaucoma, in which glaucoma was rapidly induced. However, similar findings have been reported in humans. For example, Ventura and colleagues conducted a study of 84 patients with suspected glaucoma and found a disproportionate reduction in PERG amplitude compared to RNFL thickness, supporting the concept that retinal ganglion cell dysfunction might precede permanent structural and functional changes .
The possibility of reversible RGC dysfunction has driven interest in the concepts of neuroprotection, neuroregeneration and neuroenhancement. Neuroprotection may allow preservation of retinal ganglion cells by halting the secondary cascade of glaucoma pathogenesis [28–30]. Neuroregeneration is the process of promoting the rebuilding of optic nerve axons and neuroenhancement is treatment to provide short-term improvements in function of surviving retinal ganglion cells.
The patient described in the present case presented with a visual acuity of hand movements, yet recovered 6/18 vision following trabeculectomy. In this case surgical reduction in IOP is likely to have had a neuroprotective effect, increasing the chance of preserving remaining retinal ganglion cells. However, the improvement in visual function is likely to have been due to a neuroenhancing effect of IOP reduction. Although the mechanism of improved vision cannot be proved, it is probable the reduction in IOP from the very high preoperative levels may have improved retinal ganglion cells function through restoration of axoplasmic flow and improved microcirculation to the optic nerve. Contributing factors may have included the patient’s relatively young age, high IOP and short duration of symptoms.
It is also important to acknowledge that the patient may have had an improvement in vision without surgery, and had already experienced some improvement in vision with IOP reduction with medical treatment. Unfortunately, due to the severe glaucomatous in the right eye, the visual prognosis remains poor.
In conclusion, although glaucomatous damage is deemed irreversible, our patient experienced a significant improvement in vision following successful reduction in IOP. This patient’s experience is a single case, yet it contributes to the evidence that filtration surgery may lead to functional as well as structural improvement in some patients. This may be an important consideration for future clinical studies, which tend not examine possible improvements in vision with glaucoma surgery. For example, although the Advanced Glaucoma Intervention Study (AGIS) provided evidence that trabeculectomy is an effective procedure for lowering IOP and reducing the risk of visual field progression in advanced glaucoma, the study did not report whether there was improvement in vision in any patients following surgery . This case also supports the recommendation that early surgery should be considered in patients presenting with advanced glaucomatous damage.
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
Supported in part by NHS Research Scotland Career Research Fellowship (A.J.T).
- Almasieh M, Wilson AM, Morquette B, Cueva Vargas JL, Di Polo A: The molecular basis of retinal ganglion cell death in glaucoma. Prog Retin Eye Res. 2012, 31 (2): 152-181. 10.1016/j.preteyeres.2011.11.002.View ArticlePubMedGoogle Scholar
- Yanoff M, Sassani JW: Ocular Pathology. 2014, Philadelphia: Saunders PublishingGoogle Scholar
- National Institute for Health and Clinical Excellence: CG85 Glaucoma: Diagnosis and Management of Chronic Open Angle Glaucoma and Ocular Hypertension. 2009, London: National Institute for Health and Clinical Excellence, [http://www.nice.org.uk/guidance/CG85]Google Scholar
- Gross RL, Hensley SH, Gao F, Wu SM: Retinal ganglion cell dysfunction induced by hypoxia and glutamate: potential neuroprotective effects of beta blockers. Surv Ophthalmol. 1999, 43 (S1): S162-S170.View ArticlePubMedGoogle Scholar
- Ventura LM, Venzara FX, Porciatti V: Reversible dysfunction of retinal ganglion cells in non-secreting pituitary tumors. Doc Ophthalmol. 2009, 118 (2): 155-162. 10.1007/s10633-008-9143-8.View ArticlePubMedGoogle Scholar
- Lee EJ, Kim TW, Weinreb RN, Kim H: Reversal of lamina cribrosa displacement after intraocular pressure reduction in open-angle glaucoma. Ophthalmology. 2013, 120 (3): 553-559. 10.1016/j.ophtha.2012.08.047.View ArticlePubMedGoogle Scholar
- Katz LJ, Spaeth GL, Cantor LB, Poryzees EM, Steinmann WC: Reversible optic disk cupping and visual field improvement in adults with glaucoma. Am J Ophthalmol. 1989, 107: 485-492. 10.1016/0002-9394(89)90492-3.View ArticlePubMedGoogle Scholar
- Shirakashi M, Nanba K, Iwata K: Reversal of cupping in experimental glaucoma. Ophthalmologica. 1991, 202: 194-201. 10.1159/000310198.View ArticlePubMedGoogle Scholar
- Sogano S, Tomita G, Kitazawa Y: Changes in retinal nerve fiber layer thickness after reduction of intraocular pressure in chronic open-angle glaucoma. Ophthalmology. 1993, 100: 1253-1258. 10.1016/S0161-6420(93)31497-1.View ArticlePubMedGoogle Scholar
- Kotecha A, Siriwardena D, Fitzke FW, Hitchings RA, Khaw PT: Optic disc changes following trabeculectomy: longitudinal and localization of change. Br J Ophthalmol. 2001, 85: 956-961. 10.1136/bjo.85.8.956.View ArticlePubMedPubMed CentralGoogle Scholar
- Russo A, Katsanos A, Riva I, Floriani I, Biagioli E, Quaranta L: Topographic optic disc changes after successful trabeculectomy evaluated using spectral domain optical coherence tomography. J Ocul Pharmacol Ther. 2013, 29 (10): 870-875. 10.1089/jop.2013.0127.View ArticlePubMedGoogle Scholar
- Aydin A, Wollstein G, Price LL, Schuman JS: Optical coherence tomography assessment of retinal nerve fiber layer thickness changes after glaucoma surgery. Ophthalmology. 2003, 110 (8): 1506-11. 10.1016/S0161-6420(03)00493-7.View ArticlePubMedPubMed CentralGoogle Scholar
- Robin AL, Quigley HA: Transient reversible cupping in juvenile-onset glaucoma. Am J Ophthalmol. 1979, 88 (3): 580-584. 10.1016/0002-9394(79)90518-X.View ArticlePubMedGoogle Scholar
- Quigley HA: Childhood glaucoma: results with trabeculotomy and study of reversible cupping. Ophthalmology. 1982, 89 (3): 219-226. 10.1016/S0161-6420(82)34803-4.View ArticlePubMedGoogle Scholar
- Greenidge KC, Spaeth GL, Traverso CE: Change in appearance of the optic disc associated with lowering of intraocular pressure. Ophthalmology. 1985, 92: 897-903. 10.1016/S0161-6420(85)33937-4.View ArticlePubMedGoogle Scholar
- Irak I, Zangwill L, Garden V, Shakiba S, Weinreb RN: Change in optic disk topography after trabeculectomy. Am J Ophthalmol. 1996, 122: 690-695. 10.1016/S0002-9394(14)70488-X.View ArticlePubMedGoogle Scholar
- Lesk MR, Spaeth GL, Azura-Blanco A, Araujo SV, Katz LJ, Terebuh AK, Wilson RP, Moster MR, Schmidt CM: Reversal of optic disc cupping after glaucoma surgery analyzed with a scanning laser tomography. Ophthalmology. 1999, 106: 1013-1018. 10.1016/S0161-6420(99)00526-6.View ArticlePubMedGoogle Scholar
- Leung CKS, Woo J, Tsang MK, Tse KK: Structural and functional recovery in juvenile open angle glaucoma after trabeculectomy. Eye. 2006, 20: 132-134. 10.1038/sj.eye.6701819.View ArticlePubMedGoogle Scholar
- Bevin TH, Moteno ACB, Herbison P: Otago Glaucoma Surgery Outcome Study: long-term results of 841 trabeculectomies. Clin Exp Ophthal. 2008, 36: 731-737. 10.1111/j.1442-9071.2008.01896.x.View ArticleGoogle Scholar
- Quigley HA: Neuronal death in glaucoma. Prog Retin Eye Res. 1999, 18: 39-57. 10.1016/S1350-9462(98)00014-7.View ArticlePubMedGoogle Scholar
- Kaushik S, Pandav SS, Ram J: Neuroprotection in glaucoma. J Postgrad Med. 2003, 49: 90-10.4103/0022-3859.917.View ArticlePubMedGoogle Scholar
- Swanson WH, Felius J, Pan F: Perimetric defects and ganglion cell damage: interpreting linear relations using a two-stage neural model. Invest Ophthalmol Vis Sci. 2004, 45: 466-472. 10.1167/iovs.03-0374.View ArticlePubMedGoogle Scholar
- Harwerth RS, Carter-Dawson L, Shen F, Smith EL, Crawford ML: Ganglion cell losses underlying visual field defects from experimental glaucoma. Invest Ophthalmol Vis Scie. 1999, 40: 2242-2250.Google Scholar
- Harwerth RS, Crawford ML, Frishman LJ, Viswanathan S, Smith EL, Carter-Dawson L: Visual field defects and neural losses from experimental glaucoma. Prog Retin Eye Res. 2002, 21: 91-125. 10.1016/S1350-9462(01)00022-2.View ArticlePubMedGoogle Scholar
- Marx MS, Podos SM, Bodis-Wollner I, Howard-Williams JR, Siegel MJ, Teitelbaum CS, Maclin EL, Severin C: Flash and pattern electroretinograms in normal and laser-induced glaucomatous primate eyes. Invest Ophthalmol Vis Sci. 1986, 27: 378-386.PubMedGoogle Scholar
- Marx MS, Podos SM, Bodis-Wollner I, Lee PY, Wang RF, Severin C: Signs of early damage in glaucomatous monkey eyes: low spatial frequency losses in the pattern ERG and VEP. Exp Eye Res. 1988, 46: 173-184. 10.1016/S0014-4835(88)80075-7.View ArticlePubMedGoogle Scholar
- Ventura LM, Sorokac N, De Los Santos R, Feuer WJ, Porciatti V: The relationship between retinal ganglion cell function and retinal nerve fiber thickness in early glaucoma. IOVS. 2006, 47 (9): 3904-11.Google Scholar
- Schwartz MI, Belkin M, Yoles E, Solomon A: Potential treatment modalities for glaucomatous neuropathy: neuroprotection and neuroregeneration. J Glaucoma. 1996, 5 (6): 427-432.View ArticlePubMedGoogle Scholar
- Osborne NN, Ugarte M, Chao M: Neuroprotection in relation to retinal ischemia and relevance to glaucoma. Surv Ophthalmol. 1999, 43: S102-S128.View ArticlePubMedGoogle Scholar
- Blumenthal EZ, Weinreb RN: Assessment of the retinal nerve fiber layer in clinical trials of glaucoma neuroprotection. Surv Ophthalmol. 2001, 45: S305-S312.View ArticlePubMedGoogle Scholar
- The AGIS investigators: The advanced glaucoma intervention study (AGIS): 1. Study design and methods and baseline characteristics of study patients. Control Clin Trials. 1994, 15 (4): 299-325.View ArticleGoogle Scholar
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2415/14/162/prepub
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.