Ординатура / Офтальмология / Английские материалы / Ocular Disease Mechanisms and Management_Levin, Albert_2010

Figure 40.1  External appearance of involved artery. The photo demonstrates the characteristic irregularly enlarged and ropey appearance of a giant cell arteritis-involved artery. This would typically be tender to the touch and the pulse may be decreased or absent.

Table 40.1  Characteristic symptoms and neuro-ophthalmic manifestations of giant cell arteritis

categories of subjective complaints: (1) transient visual disturbance; (2) double vision; and (3) loss of all or part of the vision in one or both eyes. The differential diagnosis for transient visual obscurations lasting several minutes includes emboli; or that lasting seconds includes swelling of the optic disc. New-onset double vision in the elderly is a common occurrence in association with medical ischemic etiologies of cranial mononeuropathies, such as hypertension or dia-

Figure 40.2  Histologic section of involved artery. In this example the lumen of the artery is nearly occluded and there is evidence for inflammatory infiltrate and giant cells.

betes. However GCA is a potential diagnosis even in the presence of these common systemic diseases and must be carefully considered in each individual patient. Permanent vision loss from GCA is most frequently associated with an arteritic form of anterior ischemic optic neuropathy (AAION) characterized by swelling of the optic disc; however, it may also be secondary to posterior ischemia of the retrobulbar optic nerve or from central retinal or cilioretinal artery occlusions (Figure 40.3).35 AAION must be differentiated from nonarteritic anterior ischemic optic neuropthy (NAION) through clinical evaluation and suspicion, an accompanying cilioretinal artery occlusion which is diagnostic of a vasculitic etiology, or through fluorescein angiography which, in the case of AAION, may demonstrate a marked delay in disc or choroidal perfusion. Formal visual field testing and analysis should be performed on any patient with suspected GCA but the defects observed may vary widely depending on the involvement of the optic nerve. Progressive loss of visual field is ominous and may be observed as evidence for worsening clinical status (Figure 40.4).

Glucocorticoids remain the primary treatment for GCA; however, the high doses and long duration that are required for effective control of disease are also associated with significant morbidity (Box 40.1). In particular, the risk of bone fractures is significant and prophylactic therapy to decrease osteoporosis should be used concomitantly with the steroid treatment. Differing opinions about the optimum initial steroid dose or route of administration remain, although there is some evidence in support for high-dose intravenous induction therapy in producing sustained remissions and decreasing the total steroid requirement.36 Steroid-sparing agents have been attempted and clinical trials report varying conclusions regarding the utility of methotrexate, although a recent meta-analysis of the published trials supports an adjunctive role for methotrexate in GCA therapy in conjunction with steroids.37 Recent interest in use of biologic agents in the treatment of immune-mediated disease prompted trials of agents that target tumor necrosis factor-α (TNF- α).38,39 There have been discordant results from the clinical trials with TNF-α blockade and there have been two case reports of individuals who developed GCA while on one of

the TNF-α blockers, supporting controversies in the utility of this therapy for control of GCA. A monoclonal antibody that targets the B-cell-associated CD20 was used in two patients to deplete B lymphocytes; respiratory complications were observed in one individual.40 In addition to steroid

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therapy, the use of aspirin has been suggested as adjunctive therapy. Retrospective studies demonstrate that low-dose aspirin may reduce risks of ischemic complications of GCA.41 Prospective controlled clinical trials will be required to assess the utility of aspirin in GCA.

Box 40.1  Giant cell arteritis (GCA) treatment

•If GCA is highly suspicious then immediate initiation of high-dose steroid therapy

No consensus re dose/route

Many recommend initiating high-dose intravenous therapy in cases of vision loss

•Biopsy is performed as soon as possible, usually within 1–2 weeks

Pathologic hallmarks may remain for a long time despite therapy

•Evaluate and treat patient for osteoporosis

•Adjunctive use of aspirin may help protect from ischemic complications

•Use of steroid-sparing agents: controversial effectiveness

Therapy is generally effective in reducing systemic symptoms of GCA such as fatigue, fever, headache, and jaw claudication and this therapeutic response is typically dramatic, occurring within hours to days of starting steroids. However, it is unusual for visual functions to recover following the onset of therapy; thus permanent vision loss remains a major complication of disease. In addition, progressive loss of vision may occur despite onset of steroid therapy, but will generally present within the first week.5 If untreated or treated with insufficient immunosuppressive therapy, then the risk for loss of vision in the fellow eye within 2 weeks following AAION in the first eye is significant.42 Long-term complications of GCA include thoracic aortic aneurysms and ischemia.

Pathology

The pathological hallmark of GCA is a granulomatous inflammatory infiltrate involving all layers of the vessel wall, in particular in the intima or media with concomitant damage or destruction of the inner elastic lamina (Box 40.2).27 The presence of giant cells is not required in order to make the diagnosis. Skip lesions, areas without apparent evidence for inflammation, can occur in 8.5–28.3% of involved specimens. Typically the inflammatory infiltrate consists of a mixture of lymphocytes, predominantly CD4+ T cells, mononuclear cells, and occasional neutrophils and eosinophils. Some pathologic findings are preserved in biopsies of individuals who have already been on prolonged steroid therapy and may be best detected using special immunohistochemical or histologic stains. Following steroid therapy, findings common to involved arteries include loss of the internal elastic lamina and infiltration of lymphocytes, mononuclear cells, and epithelioid histiocytes in a band at the junction of the outer layer of muscle and adventitia.26

Etiology

The etiology of GCA is unknown but the pathophysiology of disease is mediated by an immune mechanism. What agents could initiate or modify the disease process? Several pathogens have been implicated as potential initiat-

Pathophysiology

Box 40.2  Giant cell arteritis: pathologic diagnosis

•Large biopsy required, recommend >15 mm

Lesions may be discontinuous

All sections must be analyzed

•Giant cells identified at the junction of the intima and media

•Nonspecific inflammatory infiltrate

•Disruption of internal elastic lamina

Box 40.3  Giant cell arteritis and genetics:

possible associations

•HLA-DRB*04

•HLA-B*15

•MICA A5

•Possible polymorphisms in myeloperoxidase, matrix

metalloproteinase 9, interleukin-10, intercellular adhesion molecule 1, and Fc-γ receptor

ing agents either because of a temporal association between onset of GCA and known epidemics or because of the presence of genetic fingerprints of microbial agents in association with lesions.14 Epidemiologic studies of large populations demonstrate a temporal correlation between the onset of GCA and various acute systemic microbial diseases, including Mycoplasma pneumoniae, parvovirus B19, and Chlamydia pneumoniae, suggesting a direct or indirect effect of infection on the clinical manifestation of GCA.16,43,44 A number of candidate microorganisms have been entertained as specific inducing agents in GCA lesions. Genetic analysis of affected arteries yielded conflicting evidence for parvovirus DNA, herpesvirus zoster DNA, C. pneumoniae DNA, and yet unidentified sequences of microbial origin.44–49 The significance of the relationship of these or other microorganisms to GCA pathogenesis requires additional future investigation.

Pathophysiology

Genetic associations

Significant evidence indicates that GCA disease susceptibility is in part mediated by expression of specific major histocompatibility complex (MHC) class 1 alleles. Immunogenetic susceptibility to GCA is suggested by association with HLADRB1*04 and conservation of an antigen-binding domain of the DR4 molecule.17 Recently, independent associations of MICA A5, HLA-B*15, and HLA-DRB1*04 alleles with GCA and a synergistic increase when the MICA A5 is in combination with either the HLA-B*15 or HLA-DRB*04 alleles was observed, strengthening the associations between HLA and GCA (Box 40.3).50

Polymorphisms in genes that code for agents that either modify the immune response or are involved in local tissue damage have been a subject of recent interest as potential disease modifiers in GCA. Myeloperoxidase (MPO) is a molecule of interest in many inflammatory diseases; the -463 G/A MPO promoter polymorphism, G allele homozygosity

Section 5  Neuro-ophthalmology Chapter 40  Giant cell arteritis

is more commonly observed in individuals with GCA than in controls.51 Multiple gelatinases, including MMP 2, 9, and 14, are observed in the inflamed GCA tissues and are also suspected of playing a role in disease pathogenesis.52 In a limited sample from one institution, a polymorphism in a coding SNP of MMP-9 (rs2250889, G allele) is overrepresented in patients with GCA.20 Intercellular adhesion molecule 1 (ICAM-1) is also highly expressed in GCA lesions and there is controversy as to whether a polymorphism in exon 4 is associated with either polymyalgia rheumatica (PMR), a related systemic illness without vasculitis, or GCA susceptibility.53,54 IL-10 may act to suppress the proinflammatory cytokine IFN-γ. Two studies recently reported an increase in different polymorphisms in IL-10 in GCA patients, as compared to controls.23,25 When a polymorphism in the first intron of the IFN-γ gene was studied, there were no associations with disease susceptibility, although there was evidence for a relationship between specific alleles and disease severity supporting a potential role for disease modification by IFN-γ.22 Immune regulation is also achieved through the Fc-γ receptor and the FCGR2A-FCGR3A 131R-158F haplotype was associated with GCA susceptibility.55 In combination with HLA-DRB1*04 positivity, the presence of FCGR2A-131R was associated with a multiplicative increase in GCA susceptibility. The relevance of these observations requires additional study.

Alterations in inflammatory responses

Significant progress has been achieved on the immunophenotypic features of vascular lesions and circulating mononuclear populations of patients with GCA. This characterization provides potentially important insights about the immunopathogenesis of GCA vasculitis, and points to the unresolved issue of the antigenic target in the vascular lesions.

Distinctive patterns of cytokine production and specific, topographic localization of CD4+ T cells and CD68+ macrophages indicate an immunologically active state in GCA.56–63 Furthermore, analysis of T-cell receptors (TCR) in peripheral blood lymphocytes of GCA patients demonstrates expansion of T cells with specific TCR V domains and CD4 T-cell expansions with restricted use of Jβ genes, suggesting an antigen-specific local response.58

Examination of the cellular inflammatory infiltrate within GCA lesions primarily reveals macrophages and CD4+ T cells.62 Immunohistochemistry demonstrates the diffuse presence of IL-6- or IL-1β-expressing CD68+ macrophages.62 CD68+ cells expressing 72 kDa type IV collagenase and the inducible nitric oxide synthase (iNOS) are found in the intima and intima-media of the artery, implicating these cells in the vascular-destructive response. A chimera mouse model, in which arterial segments of human specimens were implanted into a severe combined immunodeficiency (SCID) mouse, provides information about the activity state of the resident immune cells. Adventitial dendritic cells of either PMR or GCA specimens, in contrast to normal samples, were noted to be functionally mature in their ability to stimulate T cells; suggesting that activation of these cells plays a significant role in local T-cell activation.57

In contrast to the common T-cell presence in affected arteries, B cells are infrequent in GCA lesions. However,

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identification of lesional B cells demonstrates the presence of these cells in the adventitia, both scattered and located in perivascular clusters, the same tissue microenvironment as the antigenically activated T cell. These lines of evidence strongly implicate the role of a CD4-mediated immune response in the formation of GCA vascular lesions.

Identification of the inciting antigen(s)

What is the antigenic target of this response? Evidence for a specific antigenic response in GCA comes from studies of lesional T cells.63 Clonal expansion of CD4+ T cells bearing identical specificities has been observed in independent inflammatory foci from the same individual. Proliferation studies using T-cell lines derived from GCA-involved arteries provide additional evidence for local antigen expression and validate a microbial pathogenesis hypothesis. A proliferative response of these T-cell clones is observed in response to stimulation by exposure to autologous antigen-presenting cells and tissue extracts from autologous or nonautologous GCA or PMR-derived arteries.64 Tissue extracts from control arteries did not produce T-cell stimulation of these clones. This important study provides strong evidence of local antigen expression in the arteries of both GCA and PMR. The observed stimulation is unlikely to be secondary to local, arterial cytokine production because inflammatory cytokines have been observed in arterial biopsies from patients with PMR as well as from patients with GCA. Furthermore, the antigen is not ubiquitously expressed, since stimulation is not observed with arterial extracts from normal individuals.

These findings suggest that vascular lesions are distinguished, compared to uninvolved sites, by the presence of antigenic targets for the disease-related immune response. It is conceivable that the vascular target is a self-antigen(s), somehow locally modified in the PMR and GCA arteries for immunogenicity. Such modifications might include structural changes to somatic proteins, and/or enhanced antigen-presenting capabilities of local resident or infiltrating cells of these vascular segments.29 However, the GCAassociated antigen(s) has resisted efforts towards its biochemical identification, and its restriction to inflammatory lesions would be an unusual feature for self-antigens. Accordingly, there are uncertainties regarding the existence of a GCA autoantigen, and formidable technical and experimental difficulties have precluded identification of candidates. An alternative and equally compelling hypothesis, in particular in concert with the genetic evidence for microbial sequences in GCA lesions, is that vascular microbial infection and local expression of an antigen of noneukaryotic origin drive the stimulation of lesional T-cell clones.

Role for cytokines and chemokines in disease activity

Many proinflammatory cytokines and chemokines are described in tissues and serum of patients with GCA. Some evidence points to a predictive value of the levels of these agents in defining either disease severity or response to therapy. In one study, the levels of monocyte chemoattract-

ant protein-1 (MCP-1) mRNA, as measured by quantitative reverse transcriptase polymerase chain reaction (RT-PCR), were noted to be significantly higher in individuals with GCA who experienced two relapses over the course of 1 year as compared to those in remission.65 Systemic manifestations of GCA and PMR indicate an inflammatory response characterized by activated circulating monocytes with attendant production of IL-1 and IL-6; elevations of tissueassociated IL-1β and IL-6 mRNA correlate with increased systemic inflammation. Increased lesional TNF-α mRNA is associated with a longer duration of systemic corticosteroid requirement.66

It is believed that there may be a common trigger to both GCA and PMR but that the disease phenotype is controlled by additional immunologic or regulatory factors. Studies of specific GCA lesions for cytokine profiles provide additional clues about the pathogenesis of this disease. The production of IL-6 is found in both the tissue and circulation in GCA but is restricted to the circulation in PMR. Focal immunologic activation is observed in a high percentage of GCA specimens in which IL-1β, IL-6, and T-cell-derived cytokines IL-2 and IFN-γ are observed.15,65 Although GCA lesional IFN- γ-producing cells are less than 4% of the tissue-infiltrating cells, the IFN-γ+ cells are generally CD4+ T cells (greater than 90%); these are often associated with immune-mediated diseases.63 The IFN-γ+, CD4+ T cells are mature and show evidence of recent encounters with antigen, as demonstrated by expression of CD45RO and production of IL-2 receptor (IL2R). Recently the role of IL-23, IL-17, and the Th17 subset of T cells has gained significant interest in immune pathogenesis of many inflammatory diseases. To date there are no reports for the role of these cells or cytokines in GCA pathogenesis.

Pathophysiology

Pathophysiology of GCA is likely controlled by multiple factors, including exposure to an initiating antigen, recruitment and activation of inflammatory cells, differentiation of macrophages and T lymphocytes into specific effector cells, proliferation of myoblasts with secondary luminal stenosis, and ischemia (Figure 40.5 and Box 40.4). Genetic factors initially support the ability of the affected individual to respond to the inciting agent and help direct the immune response towards a proinflammatory function. Disease activity or response results from a combination of activation of the immune system and modulation of local responses. Local modulation likely occurs through genetic polymorphisms in genes that control responsiveness to immune activation, cytokine production, and locally expressed proteins for tissue degradation or repair. Major advances in the field require a comprehensive understanding of disease triggers combined with advances in targeted control of inflammation.

Conclusion

GCA, a systemic vasculitis of older individuals, continues to be a disease that presents many diagnostic and therapeutic challenges. In the absence of the “gold standard”

V

Figure 40.5  Giant cell arteritis pathogenesis. Giant cell arteritis likely results from a multifactorial insult including genetic predisposition, exposure to specific tissue-associated antigen, local tissue factors, and immune response elements that create the inflammatory arterial milieu leading to ischemia and disease manifestations.

Box 40.4  Pathophysiology of giant cell arteritis

•Genetic susceptibility

•Environmental exposure

•Possible pathogen or local tissue antigen involvement

•Immune responsiveness

•Effector tissue damage leading to ischemia

histopathologic arterial involvement, the diagnosis is circumstantial and based on clinical presentation in combination with nonspecific indicators of inflammatory disease such as the ESR or CRP. At the present time pharmacologic therapy continues to be based on nonspecific immunosuppression, which is often associated with high morbidity in the elderly patient population, which is at greatest risk for the disease. Many clues about pathogenesis exist; however, the specific disease pathophysiology remains elusive. Advances in the scientific understanding of disease pathophysiology are required in order to improve diagnostic confidence and therapeutic options for this serious disease.

2.Gordon LK, Levin LA. Visual loss in giant cell arteritis. JAMA 1998;280:385–386.

3.Hayreh SS, Podhajsky PA, Zimmerman B. Ocular manifestations of giant cell arteritis. Am J Ophthalmol 1998;125: 509–520.

4.Gonzalez-Gay MA, Barros S, Lopez-Diaz MJ, et al. Giant cell arteritis: disease patterns of clinical presentation in a series of 240 patients. Medicine (Baltimore) 2005;84:269–276.

16.Petursdottir V, Johansson H, Nordborg E, et al. The epidemiology of biopsypositive giant cell arteritis: special reference to cyclic fluctuations. Rheumatology (Oxf) 1999;38:1208– 1212.

26.Font RL, Prabhakaran VC. Histological parameters helpful in recognising

steroid-treated temporal arteritis: an analysis of 35 cases. Br J Ophthalmol 2007;91:204–209.

29.Gonzalez-Gay MA, Lopez-Diaz MJ, Barros S, et al. Giant cell arteritis: laboratory tests at the time of diagnosis in a series of 240 patients. Medicine (Baltimore) 2005;84:277–290.

36.Mazlumzadeh M, Hunder GG, Easley KA, et al. Treatment of giant cell arteritis using induction therapy with high-dose glucocorticoids: a double-blind, placebo-controlled, randomized prospective clinical trial. Arthritis Rheum 2006;54:3310–3318.

39.Pipitone N, Salvarani C. Improving therapeutic options for patients with giant cell arteritis. Curr Opin Rheumatol 2008;20:17–22.

50.Gonzalez-Gay MA, Rueda B, Vilchez JR, et al. Contribution of MHC class I region to genetic susceptibility for giant cell arteritis. Rheumatology (Oxf) 2007;46: 431–434.

57.Ma-Krupa W, Jeon MS, Spoerl S, et al. Activation of arterial wall dendritic cells and breakdown of self-tolerance in giant cell arteritis. J Exp Med 2004;199:173– 183.

59.Weyand CM, Ma-Krupa W, Goronzy JJ. Immunopathways in giant cell arteritis and polymyalgia rheumatica.

Autoimmun Rev 2004;3:46–53.

64.Weyand CM, Schonberger J, Oppitz U,

et al. Distinct vascular lesions in giant cell arteritis share identical T cell clonotypes. J Exp Med 1994;179:951–960.

Introduction

Ischemic optic neuropathy refers to a group of conditions in which damage to the optic nerve is presumed to be secondary to ischemia of the optic nerve head (anterior ischemic optic neuropathy; AION) or retrobulbar optic nerve (posterior ischemic optic neuropathy; PION). It is clinically characterized by sudden painless loss of vision. By definition, AION presents with optic disc edema and PION without optic disc edema. AION is further subclassified as nonarteritic AION (NAION) and arteritic AION (AAION) based on the presumed underlying etiology of the latter being an inflammatory process most commonly caused by giant cell arteritis (GCA). NAION is considered to encompass diabetic papillopathy.

Nonarteritic ischemic optic neuropathy

NAION typically occurs in patients older than 50 years, with most being between 60 and 70 years.1 The incidence in Caucasian populations is about 2.3–10.3 patients per 100 000 over the age of 50 years.2,3 NAION is uncommon in patients under 50 but does occur.4 It occurs predominantly in Caucasians. The clinical features of NAION are summarized in Box 41.1.

Clinical course

Progressive NAION occurs in approximately 22–27% of patients and is defined as either stepwise, episodic decrements or steady decline of vision over weeks prior to eventual stabilization. Further decline in visual acuity after 1–2 months from initial onset is rare.5,6 The Ischemic Optic Neuropathy Decompression Trial (IONDT) reported up to 40% of patients showing an improvement of several lines of visual acuity.7 However, this apparent visual recovery may be an adaptation to the visual field defect or eccentric fixation.1 Younger patients with NAION (less than 50 years of age) have been reported to have better visual acuity outcomes.5,8

Second eye involvement occurs in approximately 15–24% of patients within 5 years of the first eye being affected.1,7,9

There is thought to be an increased incidence in second eye involvement in patients with poor visual acuity in the first eye and diabetes. However, the IONDT did not report age, sex, smoking history, or aspirin use to alter the incidence of second eye involvement. It has been suggested that younger patients may have a higher risk of fellow eye involvement than older patients, with rates of up to 35% fellow eye involvement within a median of 7 months being reported. Other investigators have suggested that higher rates of both anemia and type 1 diabetes mellitus are significantly associated with decreased time to second eye involvement in younger patients.5 The recurrence rate of NAION in the same eye is approximately 3–8% with a median follow-up of 3 years from first onset.10–12

A classic finding on the unaffected side is a small-diameter optic disc with small or absent optic cup: this is known as “disc at risk.”13 The optic disc swelling subsides between 6 and 12 weeks, with a median time of 8 weeks, after acute disc swelling, leaving a pale atrophic-appearing optic nerve head. The time to resolution of the disc edema has been shown to be longer in diabetics, but also longer in those who have milder visual loss. It seems that corticosteroid treatment may hasten the time to resolution of the disc swelling.14 Despite the retinal nerve fiber layer (RNFL) loss that occurs after NAION, excavation of the optic cup is rarely detected, as opposed to eyes with AAION, in which it is the most common end-stage appearance.15

Investigations

The diagnosis of NAION is based on clinical history and examination and there are no specific tests to confirm the diagnosis. The differential diagnosis includes an extensive list of causes of unilateral optic disc swelling (rarely, bilateral). The three most important differential diagnoses to consider are AAION secondary to GCA, and optic neuritis (Box 41.2). Figure 41.1 demonstrates the different appearance between the optic nerve head appearance in NAION and AAION.

Neuroimaging

There are a few magnetic resonance imaging (MRI) studies evaluating small series of patients with NAION.16,17 Unlike patients with optic neuritis who had abnormal MRI in 97% of cases, patients with NAION only had an abnormal scan in 17%.18 There are more white-matter abnormalities in

Section 5  Neuro-ophthalmology Chapter 41  Ischemic optic neuropathy

patients with NAION, suggesting that it is more likely in the setting of diffuse cerebrovascular small-vessel disease.19 Eyes with NAION have more white-matter hyperintensities, lower optic nerve volume, and magnetization transfer ratio of the chiasm than controls, likely reflecting axonal loss and demyelination.20

as reduced amplitude in the involved eye, and the uninvolved eye is commonly abnormal. The N95 component of the pattern electroretinogram (PERG) may be reduced in ischemic optic neuropathy,23 while the P50 component of the PERG is more frequently affected in NAION than demyelination.24

Electrophysiology

Both arteritic and nonarteritic ION have been shown to result in amplitude reduction in pattern visual evoked potential (VEP) and flash VEP.19,21,22 This contrasts with demyelination in which there is delayed latency as well

Box 41.1  Clinical features of nonarteritic anterior

ischemic optic neuropathy

Quantitative ocular imaging modalities

Quantitative techniques that measure the peripapillary RNFL thickness and/or optic disc morphology, such as optical coherence tomography (OCT, StratusOCT), scanning laser polarimetry (SLP), and confocal scanning laser ophthalmoscopy (Heidelberg Engineering retinal tomography; HRT) have been used to evaluate the optic disc and RNFL in NAION. Presently, these techniques do not assist in diagnosis or management but they may offer a quantitative measurement of ganglion cell loss in the pale optic disc and may be useful in the evaluation of patients with NAION after swelling of the optic disc has resolved.

Several studies have evaluated the correlation between RNFL thickness and visual field sensitivities using these modalities. It has been demonstrated that both SLP and OCT show strong correlations between RNFL thickness, and visual sensitivities.25–27 OCT has also demonstrated that some patients develop subretinal fluid following NAION. The resolution of the subretinal fluid may explain some of the visual recovery that has been documented to occur.28 The HRT has also been used to evaluate the morphology of the optic nerve head cup and disc and has shown that eyes that have had an episode of AAION show greater excavation than eyes with NAION.29 A possible explanation is that in AAION the ischemic insult is more severe compared to NAION and consequently leads to more tissue damage. Alternatively, it may be that excavation in eyes with NAION is more difficult to detect because of the previously small or absent physiologic cup and the development of optic disc pallor (Figures 41.2–41.5).

y [mm]

2.50

–0.50

Figure 41.4  (A) Serial enlargement of the cup:disc ratio in a patient who had an episode of right arteritic anterior ischemic optic neuropathy as measured by the Heidelberg retina tomograph. The first image (1) was taken at 1 month and each serial image was taken monthly. (B) Change in the cup:disc ratio of the involved compared to the contralateral uninvolved eye.