Glaucomatous Optic Atrophy


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Glaucomatous Optic Atrophy

  1. 1. 1 4 April 2011 Glaucomatous Optic Atrophy John R. Martinelli, OD, FAAO St. George’s University School of Medicine Abstract Glaucomatous optic atrophy (GOA) can be characterized as an irreversible, end-stage glaucomatous optic neuropathy with associated severe visual field loss and reduction of acuity. Clinically apparent is advanced optic cupping, loss of neuro-retinal rim tissue, and optic pallor. This degree of optic neuropathy and functional vision loss can be secondary to various contributing factors including an undiagnosed, poorly managed, or poorly controlled primary or secondary glaucoma. The development of glaucomatous optic atrophy in properly managed cases, and particularly in normal tension glaucoma (NTG), may also be related to genetic factors or generalized systemic or vascular disease jeopardizing the integrity of the optic nerve and ocular micro-circulation. Poor patient compliance with treatment is another consideration which may lead to eventual end-stage disease. The pathogenesis and pathophysiology of secondary glaucomatous optic atrophy can be distinguished from other forms of optic atrophy with respect to etiology and clinical manifestations. Keywords: Glaucoma, GOA, Glaucomatous Optic Atrophy, Glaucomatous Optic Neuropathy, ION, Ischemic Optic Neuropathy, NTG, Normal Tension Glaucoma, Secondary Optic Atrophy
  2. 2. 2 Introduction Glaucomatous optic atrophy (GOA) is classified as a secondary optic atrophy arising from contributing ocular or systemic disease. This is in contrast to the primary optic atrophies, such as Leber’s hereditary optic atrophy or autosomal dominant optic atrophy (ADOA), which are attributed to inheritance with a molecular-genetic basis. Clinically, the optic disc can appear with peripapillary chorio-retinal atrophy, a large vertical cup/disc ratio, thinning or absence of neuro-retinal rim tissue, associated NFL defects, and marked optic pallor. Alternatively, a small or hypoplastic optic nerve without cupping can be susceptible to end-stage glaucomatous optic atrophy with pallor due to morphologic disadvantages. An afferent pupillary defect will be present in the affected eye along with significant loss of visual field and acuity with no-light-perception (NLP) possible. The pathogenesis of this disorder and subsequent loss of optic nerve function can be the end result of various etiologies including an uncontrolled longstanding primary glaucoma. Examples include chronic open angle glaucoma (COAG), chronic mixed mechanism or narrow angle glaucoma (NAG), and chronic or acute angle closure glaucoma (ACG). Uncontrolled secondary glaucoma’s such as uveitic glaucoma, traumatic angle recession glaucoma, neovascular glaucoma (NVG), pseudoexfoliative glaucoma (PXE), phacomorphic glaucoma, pupillary block glaucoma, and surgical or iatrogenic induced glaucoma are also examples which can lead to end stage disease. Medications such as Prednisone and Topamax (Topiramate) can create ocular hypertensive conditions leading to secondary glaucoma which may induce optic atrophy as well. The irido-corneal-endothelial (ICE) syndromes such as Chandler’s syndrome are an example of congenital anterior segment disorders which can lead to secondary glaucoma and optic atrophy if left undetected or uncontrolled. Systemic conditions affecting the integrity of the optic disc, neuro-retinal rim, or retinal nerve fiber layer (RNFL) will also provide opportunity for glaucomatous optic neuropathy leading to atrophy. Vascular disease such as carotid insufficiency creating ischemic conditions at the level of the optic nerve can contribute to glaucomatous optic atrophy even at normal intraocular pressures. Systemic inflammatory disease including giant cell arteritis (GCA) is another example that may produce ocular ischemia and greater risk. Orbital compressive disease such as advanced thyroid ophthalmopathy or orbital melanoma with optic nerve involvement is also considered a risk factor for associated secondary glaucomatous optic atrophy. Considering the multitude of possible clinical scenarios and etiologies, a thorough understanding of related ocular and systemic disease is critical in recognizing and identifying those individuals at risk. Aggressive medical and/or surgical therapy must be instituted before atrophic progression and irreversible vision loss results.
  3. 3. 3 Case Report A 48 year old African-American gentleman presented to our center on August 8, 2005 as a new patient for a routine examination. He had no complaints but stated he “needed new glasses”. He reported an unremarkable ocular and systemic history. He was not aware of a family history of ocular or systemic disease. With refraction, best corrected VA was 20/20 OD and 20/30 OS without PH improvement. Keratometry did not show evidence of irregular corneal cylinder or distortion in either eye. Ishihara color plates were normal OU. Stereopsis was normal. Confrontation visual fields suggested a generalized 360 degree constriction OU. Pupils were equal, round, and responsive to light and accommodation, however, a slight grade I afferent pupillary defect (APD) was elicited OS. Extraocular muscles were full without restriction or subjective diplopia. Red cap test was diminished OS when compared with the fellow eye. Biomicroscopic examination revealed a healthy anterior segment with wide open, grade IV angles by Vonherrick technique OU. There was no evidence of keratopathy, corneal edema, anterior uveitic disease, posterior synechia, pupillary block, or lenticular changes in either eye. Intraocular pressure by Goldmann applanation tonometry was markedly elevated at 42mm Hg OD and 49mm Hg OS. Sonogage central corneal pachymetry readings were above average at 586µ OD and 599µ OS. Goldmann three mirror gonioscopy also showed an open grade IV anterior chamber in all 4 quadrants of each eye. Schwalbe’s line, trabecular meshwork, Schlemm’s canal, scleral spur, and ciliary body were viewable in each quadrant OU. There was no sign of peripheral anterior synechia (PAS), iris strands, or angle recession in either eye. Grade II pigment was apparent within the trabeculum OU without evidence of pseudoexfoliative debris in either eye. Dilated 90D ophthalmoscopic evaluation demonstrated a clear vitreous without evidence of cells or posterior inflammatory activity OU. The peripheral retina, vessels, and macula appeared healthy; however, there was dramatic optic cupping evident in each eye along with mild parapapillary atrophy present OU. A c/d of 0.7/0.8 OD and 0.9/0.9 OS was viewed with loss of neuro-retinal rim tissue more evident in the left eye. Early optic pallor was observed OS. Optic nerve head Heidelberg retinal tomography (HRT) analysis produced results corresponding to advanced glaucomatous cupping with significantly reduced rim area, volume, and thickness in each eye. Notably, the OS was quite reduced in comparison with the fellow eye and far outside of normal parameters. The same was found for the global cup shape measure (CSM) in each eye with the OS CSM confirming more advanced disease progression in that eye. Considering the above findings, a diagnosis of advanced chronic open angle glaucoma with glaucomatous optic neuropathy OU and early secondary glaucomatous optic atrophy OS was determined. He was started on Travatan (Travoprost 0.004%) 1gtt HS OU and was educated regarding the advanced stage of the disease. The likelihood of adjunctive topical treatment was discussed as was the importance of compliance and follow-up visits. SLT laser treatment was also recommended for each eye with the left eye scheduled to be performed at his first follow- up visit. Depending on the efficacy of in-office therapy, the possibility of additional surgical treatment such as endoscopic cyclophotocoagulation (ECP) or trabeculectomy
  4. 4. 4 would be considered. He was scheduled for a 1 week follow-up visit to re-assess his IOP, perform formal threshold visual field testing, and proceed with SLT treatment OS. Follow-up #1 Unfortunately, he returned approximately 1 ½ years later on February 20, 2007 with a chief complaint of “cannot see out of my left eye and my glasses don’t help”. He conveyed that because “the drops didn’t help”; he never returned for his follow-up visit and had only used the drops for a few days. His ocular and systemic history was otherwise unchanged and unremarkable. With a new refraction, best corrected VA’s were 20/20 OD and 20/CF@10’ OS without PH improvement. Pupils were equal, round, and responsive to light and accommodation, however, a dramatic grade IV APD OS was now apparent. Versions were full with good alignment and without subjective diplopia. Biomicroscopic examination remained unremarkable with grade IV angles in each eye via Vonherrick technique. Goldmann applanation tonometry was elevated at 37mm Hg OD and 38mm Hg OS. Digital stereophotography of the optic discs revealed advanced end-stage glaucomatous optic cupping OU, greater OS, with predominant optic pallor OS. The infero-temporal cupping in the right eye showed quite dramatic progression as did the degree of optic pallor present in the left eye. Optic nerve head HRT analysis demonstrated advancement of all parameters, confirming progression of the neuropathy in each eye and secondary atrophy
  5. 5. 5 in the left eye. Oculus 30-2 threshold visual field exhibited a characteristic glaucomatous Bjerrum scotoma along with an extensive peripheral nasal depression with corresponding probability map defects OD. The OS visual field was unobtainable due to his non- responsiveness to testing due to CF acuity.
  6. 6. 6 The severity of progression and danger of continued loss of vision was once again explained. He was placed on Cosopt (Dorzolamide 2%/Timolol 0.5%) 1gtt Q12H OU and Travatan Z (Travoprost 0.004%) 1gtt HS OU. He was also scheduled for 360º SLT laser treatment in each eye, with the left eye performed first at his 1 week follow-up visit. Follow-up #2 He returned on schedule for his 1 week follow-up visit and reported proper compliance with his topical treatment. Corrected VA remained 20/20 OD and 20/CF@10’ OS. Goldmann applanation tonometry showed a greatly reduced IOP of 21mm Hg OD and 26mm Hg OS. A 400µ/100 spot SLT treatment @ 40mw was applied 360º to the OS trabeculum. To enhance the post-operative effect, he was not placed on any additional topical medications and was instructed to continue his current therapeutic regimen. He was scheduled for a 10 day follow-up visit for repeat IOP measurements and OD SLT treatment. Follow-up #3 He returned as scheduled for his 10 day follow-up visit. He maintained proper compliance with his topical treatment. Corrected VA was stable at 20/20 OD and 20/CF@10’ OS. IOP OD was slightly less at 20mm Hg. The OS demonstrated a noticeable response s/p SLT treatment at 21mm Hg, representing a nearly 20% reduction. A 400µ/100 spot SLT treatment @ 40mw was also applied 360º to the OD trabeculum. His post-operative instructions were identical to the other eye without additional topical treatment recommended. He was scheduled for a 10 day follow-up visit for IOP measurements. Follow-up #4 He returned on schedule for his 10 day follow-up visit reporting good compliance with his topical treatment. Corrected VA was unchanged at 20/20 OD and 20/CF@10’ OS. IOP OD was 17mm Hg s/p SLT treatment, a 15% improvement. IOP OS was slightly less at 20mm Hg. Considering the advanced stage of progression with secondary optic atrophy, a target pressure of ≤ 12 was recommended despite a favorable response to the current treatment. Therefore, he was additionally placed on Alphagan P (Brimonidine 0.15%) 1 gtt Q12H OU and instructed to continue his other current topical medications. He was asked to return again in 1 week to re-assess his IOP and consider further treatment options.
  7. 7. 7 Follow-up #5 He returned as scheduled for his 1 week follow-up IOP check. He was now compliant with all topical medications including Cosopt, Alphagan P, and Travatan. IOP OD continued to drop to 15mm Hg. IOP OS was now at 17mm Hg. To achieve our target pressure goal of ≤ 12 OU, the possibility of requiring either surgical ECP or trabeculectomy was explained. Considering his much improved condition and the possibility of further IOP reduction often seen several weeks s/p SLT treatment, it was recommended to re-evaluate his IOP after a one month period while maintaining his current treatment regimen. He was scheduled for this visit and was again reminded of the importance of treatment. Discussion As exhibited in this case, the formation of progressive secondary glaucomatous optic atrophy (GOA) can be a visually devastating result of patient non-compliance to therapy. Early detection and optimal treatment of underlying contributing ocular and systemic conditions is critical to its prevention. Based on recent epidemiologic analyses of the primary glaucoma’s, progression to this advanced stage of pathology leading to blindness will continue to become more prevalent. By 2010, 60 million people will have open angle glaucoma (OAG) and angle closure glaucoma (ACG), and it will be the second leading cause of world blindness.1 The number estimated blind from OAG in 2010 is 4,472,083 and from ACG is 3,936,241 for a combined total of 8,408,324.1 While only 24% of those with primary glaucoma have ACG, the number of ACG blind is nearly equal to that of OAG because of the greater estimated morbidity of this disease.1 Predictive factors leading to progression in OAG have been found to vary depending on the level of intraocular pressure during the course of the disease. For patients with elevated intraocular pressure, significant predictive factors for eventual progression were older age, advanced perimetric damage, smaller neuroretinal rim, and larger area of beta zone of parapapillary atrophy.2 In contrast, patients with normal intraocular pressures, a significant predictive factor was the presence of disc hemorrhages at baseline.2 Within patients with elevated intraocular pressure, primary open-angle glaucoma and secondary open-angle glaucoma results did not differ in predictive factors for progression.2 In addition, progression of glaucomatous optic nerve head changes in OAG has been found to be independent of the size of the optic disc and alpha-zone of parapapillary atrophy and retinal vessel diameter.3 Many ocular or systemic conditions affecting the integrity of the optic nerve can lead to glaucomatous optic neuropathy with potential for end stage disease and blindness. The pathogenesis may involve several inter-related factors including structural effects of the optic nerve related to intraocular pressure, inherent susceptibility of the optic nerve itself, micro-vascular pathology or ischemia at the level of the optic nerve, as well as orbital disease.
  8. 8. 8 With respect to high-pressure related OAG, characteristic histopathologic features have been described leading to atrophy even in the absence of cupping. Diffuse and centrally intense hydropic axonal degeneration and central blocked retrograde axoplasmic transport explain loss of central acuity, generalized contraction of visual field, and generalized optic atrophy without glaucomatous cupping in eyes with prolonged high- pressure secondary glaucoma.4 Recent research has found genetic factorial influences in progressive normal-pressure or normal-tension open angle glaucoma (NTG). Examples include the optic atrophy 1 gene (OPA1) IVS 8 +32 T/C polymorphism, which has been associated with secondary glaucomatous optic atrophy in NTG and may be used as a marker for this disease association.5 This polymorphism also influences the phenotypic feature in patients with high tension glaucoma (HTG) and should be considered a genetic risk factor not only for NTG, but also for HTG.5 Individuals with an E50K mutation in the optineurin gene (OPTN) were found to have NTG that appeared to be more severe than in a control group of subjects with NTG without this mutation.6 A mutation of the GLC1A gene has also been implicated in the formation of NTG and HTG.7 Systemic cardio-vascular disease, circulatory insufficiency, ischemia, diabetes, and hypertension are examples that can have a direct affect on optic nerve function and possibly propagate glaucomatous progression to optic atrophy. Generalized inflammatory or auto-immune conditions can be a contributor to end stage disease as can systemic metabolic disorders. Orbital retro-bulbar compressive optic neuropathies will also pre- dispose the eye to GOA. Examples include conditions such as carotid stenosis leading to non-arteritic ischemic optic neuropathy (NAION) which will pre-dispose the optic disc to secondary glaucomatous optic atrophy. Giant cell arteritis (GCA) with associated temporal arteritis (TA) can create pathology producing arteritic ischemic optic neuropathy (AION) which will likewise only initiate or enhance progression. Elevated blood-serum levels of C-reactive protein (CRP), an inflammatory marker linked with atherosclerotic vascular disease, may also be a sign of ocular ischemia potentially advancing the disease.8 Metabolic syndrome and insulin resistance have been associated with diurnal variations in IOP which may have an implication in allowing progression to glaucomatous optic atrophy.9,10 Advanced orbital thyroid disease leading to Grave’s ophthalmopathy with retro-bulbar compressive optic neuropathy is an example which can mechanically allow for glaucomatous progression as well. Unfortunately, there is no treatment to reverse the effects of secondary end-stage glaucomatous optic atrophy. In its most advanced state, visual acuity and visual field loss can decline to a no-light-perception (NLP) level. Aggressive ocular and systemic treatments are preventative measures and must be instituted in high-risk individuals before atrophic progression. Preventative therapy includes topical ocular hypotensive medications providing for maximum lowering of IOP. Target pressures must be set significantly lower at the onset of treatment to provide optimal protection. In high risk individuals, at least 30% - 35% reductions with IOP’s consistently ≤ 12mm Hg is not an unreasonable goal to attain.
  9. 9. 9 Pachymetry measurements indicating reduced central corneal thickness and the possible associated RNFL implications must also be considered in the aggressiveness of the treatment plan. Caution must be noted with the beta-blockers in the event of contraindicative systemic conditions such as cardio-vascular or pulmonary disorders which may very well be present in advanced optic nerve disease. Likewise, the prostaglandin analogues must be avoided in the case of the uveitic glaucoma’s. However, at risk NTG individuals may have additional benefits with prostaglandin analogue treatment as there has been some evidence in the literature suggesting increased ocular bloodflow.11 Depending on the form of glaucoma and responsiveness to medical treatment, selective laser trabeculoplasty (SLT), argon laser trabeculoplasty (ALT), or peripheral iridotomy (PI) are also options. If in-office therapy proves to be inadequate, out-patient surgical procedures such as endoscopic cyclophotocoagulation (ECP) or trabeculectomy may be alternatives for proper pressure control. Equally important is working in conjunction with the primary care physician and appropriate medical specialists. The ultimate goal of systemic treatment is allowing for and maintaining proper ocular hemodynamics, ocular profusion, structure, and thus integrity of the optic nerve as it relates to generalized pathology. Conclusion The development of end-stage secondary glaucomatous optic atrophy leading to permanent vision loss is a disease process which may be proceeding at many levels. Certain ocular, genetic, and systemic conditions are most probably intertwined depending on the individual. The goal of therapy is to prevent progression and subsequent irreversible loss of vision. Therefore, a multi-disciplinary approach for the prevention, control, and management of the at-risk patient is mandatory. The importance of aggressive ocular treatment, proper diagnostic laboratory studies, and possibly genetic counseling must not be underestimated. The prompt initiation or maintenance of treatment for contributing systemic conditions is crucial as is the timely and proper communications with appropriate members of the health care team. Finally, as evident in this case, patient communication, understanding, compliance, and follow-up care are critical to the final outcome.
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