Macular Ganglion Cell Complex Reduction Preceding Visual Field Loss in a Patient With Chiasmal Compression With a 21-Month Follow-Up

Letters to the Editor 4. Bollinger K, Lee MS. Recurrent visual field defect and ischemic optic neuropathy associated with tadafil rechallenge. Arch Ophthalmol. 2005;123:400-401. 5. Pomeranz HD, Bhavsar AR. Nonarteritic ischemic optic neuropathy developing soon after use of sildenafil (Viagra): a report of seven new cases. J Neuroophthalmol. 2005;25:9-13. 6. Kruger JM, Pomeranz HD. Nonarteritic anterior ischemic optic neuropathy and erectile dysfunction drugs: is there an elephant in the bedroom? J Neuroophthalmol. 2017;37:104-105. Case of Bilateral Sequential Nonarteritic Ishemic Optic Neuropathy After Rechallenge With Sildenafil: Comment NAION in which associated sexual activity was specifically denied. We simply suggest that sexual activity itself may be another independent risk factor for NAION. Howard D. Pomeranz, MD, PhD Department of Ophthalmology, Northwell Health, Great Neck, New York I n their letter to the editor, Neufeld and Warner (1) present a fourth case of PDE-5 inhibitor-associated NAION with rechallenge effect. Although we appreciate their reference to our publication, we find it puzzling that they do not address the very question that we advocated exploring in such cases. What was the sexual history of their patient? Sexual intercourse itself has a plausible mechanism to provoke NAION through postcoital hypotension. The argument by Neufeld and Warner that sildenafil was the cause of the NAION would be better substantiated if they confirmed that there was no associated sexual activity. Regardless, their case does not conflict with our position. In our letter, we acknowledged evidence to implicate the drug itself including several reports of PDE-5 inhibitor-associated Macular Ganglion Cell Complex Reduction Preceding Visual Field Loss in a Patient With Chiasmal Compression With a 21Month Follow-Up T ieger et al (1) reported a series of 23 patients with chiasmal compression evaluated with optical coherence tomography (OCT) and standard automated perimetry (SAP) before and after surgical treatment. Because some of their patients showed complete visual field (VF) recovery despite persistent retinal ganglion cell (RGC) layer thinning on OCT, the authors suggested that RGC loss may precede VF loss, at least when assessed with standard 24-2 or 30-2 threshold strategies. Two invited commentaries pointed out that this is still an unsettled issue regarding compressive disorders of the anterior visual pathway (2,3). I had the opportunity to assess a patient with a pituitary tumor compressing the chiasm, followed for 21 months with OCT, SAP, and manual Goldmann perimetry (GP). My findings strongly support those of Tieger et al. A 56-year-old woman was seen for a follow-up examination because of a nonsecreting pituitary adenoma mildly compressing the optic chiasm. The adenoma was discovered 8 years previously when MRI was obtained for her menstrual 124 Joshua Kruger, MD, PhD Department of Ophthalmology, Hadassah Medical Center, Jerusalem, Israel The authors report no conflicts of interest. REFERENCE 1. Neufeld A, Warner J. Case of bilateral sequential nonarteritic ischemic optic neuropathy after rechallenge with sildenafil. J Neuroophthalmol. 2018;38:123-124. irregularities. At that time, the patient had no visual complaints, visual acuity (VA) was 20/20 bilaterally, and the remainder of the ophthalmic examination, including ophthalmoscopy, was normal. SAP (24-2 Swedish Interactive Threshold Algorithm standard test on the automated perimeter) and GP using the I/4e, I/3e, I/2e, and I/1e targets (with kinetic and central static presentations) were also normal. The patient opted for conservative management with visual and neuroimaging re-evaluation every 6 months. Five years later, with the patient still asymptomatic, bilateral VF defects to the I/2e and I/I3 isopters were detected using GP. MRI showed a small hemorrhage within the pituitary tumor, but the patient declined surgery. Six months later, VF improvement was observed, attributed to slight tumor shrinkage found on MRI. She was followed at 6-month intervals, with minimal VF depression (on both perimeters) in the upper temporal quadrant of each eye. Six years after initial evaluation, the patient's acuity remained 20/20 bilaterally, VFs were stable (Fig. 1A), and OCT (3D OCT-2000; Topcon Corp, Tokyo, Japan) in each eye was performed. It showed the peripapillary retinal nerve fiber layer (RNFL) to be within normal limits, but the RGC-inner plexiform layer (IPL) in the macular area displayed few points of significant reduction in each nasal hemiretina (Fig. 1A). The GP showed a few points of Letters to the Editor: J Neuro-Ophthalmol 2018; 38: 122-133 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Letters to the Editor FIG. 1. Results of automated visual fields and optical coherence tomography obtained 6 (A), 7 (B), and 8 (C) years after initial neuro-ophthalmic evaluation. OD, right eye; OS, left eye; GCL, ganglion cell layer; MD, mean deviation; RNFL, retinal nerve fiber layer. missing static presentation to the I/1e target (Fig. 2A). Nine months later, repeat VF examination showed slightly better results on SAP (Fig. 1B), although testing on the GP was unchanged as was the tumor size on MRI. However, OCT revealed a slight reduction of peripapillary RNFL thickness Letters to the Editor: J Neuro-Ophthalmol 2018; 38: 122-133 and a larger area of RGC-IPL reduction in each macula (Fig. 1B). One year after that, VA was 20/20 bilaterally, and SAP findings were slightly worse in the right eye and unchanged in the left eye (Fig. 1C). On OCT, there was further thinning of the peripapillary RNFL and of the 125 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Letters to the Editor FIG. 2. Kinetic (Goldmann) perimetry findings obtained 6 (A) and 8 (B) years after initial neuro-ophthalmic examination. OD, right eye; OS, left eye. RGC-IPL in each nasal hemiretina (Fig. 1C). The GP showed slight progression of VF loss, greater in the right eye (Fig. 2B). To determine RGC-IPL thickness per quadrant (a feature not available on the OCT), raw data were exported to a personal computer and analyzed using Orion OCT image analysis TABLE 1. Sequential measurements of RGC-IPL thickness Inner Circle Measurements (mm) SN Initial OCT OD OS 9 mo later OD OS 21 mo after initial OCT OD OS % reduction* OD OS IN ST Outer Circle Measurements (mm) IT SN IN ST IT 84 86 82 87 85 85 86 86 76 77 73 74 70 72 70 70 57 81 67 76 74 82 89 80 70 72 70 67 69 70 70 70 55 69 58 65 72 77 80 80 66 67 70 65 61 71 65 67 34.5 19.8 29.3 25.3 15.3 9.4 13.2 13.0 4.3 12.2 12.8 1.4 7.0 7.0 7.1 4.3 The percentage reduction between the last and first measurements of each parameter is provided. *Difference between the last and first measurements, covering an interval of 1 year. IN, inferonasal quadrant; IPL, inner plexiform layer; IT, inferotemporal quadrant; OCT, optical coherence tomography; OD, right eye; OS, left eye; RGC, retinal ganglion cell; SN, superonasal quadrant; ST; superotemporal quadrant. 126 Letters to the Editor: J Neuro-Ophthalmol 2018; 38: 122-133 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Letters to the Editor software (Orion; Voxeleron LLC, Pleasanton, CA). These values were calculated in a circular fashion, according to the Early Treatment Diabetic Retinopathy Study, but rotated (45°) to provide quadrantic measurements respecting the vertical and horizontal meridians. After excluding the fovea, values were calculated for the inner and outer segments of each quadrant. A comparison of the first and last OCT measurements showed RGC-IPL reduction in the 4 nasal quadrantic measurements ranging from 11% to 34.5%, right eye, and from 12.2% to 25.3%, left eye. A small percentage thickness reduction was also found in the temporal inner segments bilaterally (Table 1). Several studies evaluating patients with VF defects from chiasmal compression have shown that peripapillary RNFL thickness and macular RGC layer thickness are significantly correlated with VF loss on SAP (4-8) and that patients with less structural damage experience greater visual improvement after chiasmal decompression (5-7). In many patients, VF improvement, despite persistent retinal structural damage, may be attributed to restoration of transmission of neuronal impulses in axons that remain viable (2). This had led to the concept that in compressive optic pathway lesions, functional VF loss precedes structural loss, a rationale challenged by the findings of Tieger et al (1). Our patient's preference for conservative management made it possible to compare VF and OCT data prospectively over an almost 2-year (21-month) follow-up period. There was mild deterioration of the VFs over this time period, yet OCT data (especially RGC-IPL thickness) displayed definite worsening in both eyes. Horton (2) suggested that the conventional size III target used in SAP may not be sensitive enough to detect subtle VF loss. The VF results in our patient support this, as the field loss was only well defined using size I (0.25 mm2), I/2e, and I/1e targets on careful GP in the right eye. Also, it is important to notice that even on GP, progressive visual loss was not clearly defined, despite definite reduction of the RGC layer in the left eye. Therefore, it is likely that in chronic compressive lesions, retinal structures are impaired before clinically detectable VF loss. Our findings suggest that structural retinal measurements in addition to VF testing are a useful aid in the diagnosis and follow-up of patients with compressive lesions of the anterior visual pathway. Macular Ganglion Cell Complex Reduction Preceding Visual Field Loss in a Patient With Chiasmal Compression With a 21-Month Follow-Up: Comment W e appreciate Dr. Montiero's comments sharing his experience with ganglion cell loss from compressive lesions. We did observe that patients can have normal visual fields and no symptoms, despite what seems to be rather severe ganglion cell complex (GCC) thinning on optical coherence tomography (OCT) both before Letters to the Editor: J Neuro-Ophthalmol 2018; 38: 122-133 Mário Luiz Ribeiro Monteiro, MD, PhD Division of Ophthalmology (MLRM), University of São Paulo Medical School, São Paulo, Brazil Supported by a grant from Conselho Nacional de Desenvolvimento Científico e Tecnológico (No. 307393/ 2014-3), Brasilia, Brazil. The author reports no conflicts of interest. REFERENCES 1. Tieger MG, Hedges TR, Ho J, Erlich-Malona NK, Vuong LN, Athappilly GK. Ganglion cell complex loss in chiasmal compression by brain tumors. J Neuroophthalmol. 2017;37:7-12. 2. Horton JC. Invited commentary: ganglion cell complex measurement in compressive optic neuropathy. J Neuroophthalmol. 2017;37:13-15. 3. Costello F. Invited commentary: form versus function: a state of disunion? J Neuroophthalmol. 2017;37:15-16. 4. Monteiro ML, Costa-Cunha LV, Cunha LP, Malta RF. Correlation between macular and retinal nerve fibre layer Fourier-domain OCT measurements and visual field loss in chiasmal compression. Eye (Lond). 2010;24:1382-1390. 5. Danesh-Meyer HV, Papchenko T, Savino PJ, Law A, Evans J, Gamble GD. In vivo retinal nerve fiber layer thickness measured by optical coherence tomography predicts visual recovery after surgery for parachiasmal tumors. Invest Ophthalmol Vis Sci. 2008;49:1879-1885. 6. Moon CH, Hwang SC, Ohn YH, Park TK. The time course of visual field recovery and changes of retinal ganglion cells after optic chiasmal decompression. Invest Ophthalmol Vis Sci. 2011;52:7966-7973. 7. Ohkubo S, Higashide T, Takeda H, Murotani E, Hayashi Y, Sugiyama K. Relationship between macular ganglion cell complex parameters and visual field parameters after tumor resection in chiasmal compression. Jpn J Ophthalmol. 2012;56:68-75. 8. Monteiro ML, Hokazono K, Fernandes DB, Costa-Cunha LV, Sousa RM, Raza AS, Wang DL, Hood DC. Evaluation of inner retinal layers in eyes with temporal hemianopic visual loss from chiasmal compression using optical coherence tomography. Invest Ophthalmol Vis Sci. 2014;55:3328-3336. and after decompression of the chiasm (1). However, patients can have visual field loss and symptoms before structural changes are observed from axonal compression or, more specifically, because of reversible distortion of the nodes of Ranvier (2). Therefore, visual field testing in patients with compressive lesions remains very important. Because OCT is an easier test for patients and is objective, we believe that OCT should also be used in the detection of compressive lesions and during followup of affected individuals, especially because we and Dr. Montiero have shown that GCC loss can precede visual field loss. 127 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.