Leber's Hereditary Optic Neuropathy Masquerading As Retinal Vasculitis

CASE REPORTS AND SMALL CASE SERIES

of the choroid and retina, fluid The aspirate showed gram-positive Bacillus cereus posterior to the sclera, inflamed rods, and the culture revealed B ce- Endophthalmitis extraocular muscles, and a nondis- reus/Bacillus thuringiensis. Intrave- Secondary to Self-inflicted placed lens. nous vancomycin hydrochloride, Laser iridotomy, topical cy- ceftriaxone sodium, and clindamy- Periocular Injection cloplegics, and steroids failed to cin phosphate supplemented intra- reduce the intraocular pressure or vitreal injections of vancomycin and Endophthalmitis is an ocular emer- reverse the ocular inflammation ceftazidime. A normal echocardio- gency that can have a devastating out- (Figure 1). On the second day, an gram ruled out a cardiac source of come. The poor prognosis is often re- orbital computed tomography scan bacteria. On the fourth day, spon- lated to rapid progression of the demonstrated marked scleral thick- taneous scleral perforation oc- disease process and a relative delay ening, enlarged extraocular muscles, curred with extrusion of purulent in diagnosis due to the wide array of and subluxation of the lens uveal contents. The eye was eviscer- clinical symptoms and signs.1 Al- (Figure 2). Suspicion of endoph- ated. Weeks later, 2 prison guards though endophthalmitis is most of- thalmitis led to vitreous aspiration. reported to a case worker that prior ten related to surgical intervention, endogenous sources are identified in 2% to 15% of cases.1 Intravenous drug-related endophthalmitis is most commonly caused by Bacillus cereus.2,3 We report a case of B cereus endophthalmitis secondary to periorbital drug injection that resulted in spontaneous lens subluxation. This case underscores the difficulty in making an expeditious diagnosis when there is an uncertain medical history.

Report of a Case. A 29-year-old male prison inmate had a 12-hour history of vomiting associated with pain, redness, and impaired vision of the left eye. The patient denied trauma and drug abuse. Medical history was remarkable for active in- terferon therapy for hepatitis C. The Figure 1. Scleritis (T sign) and normal lens position on day 1 (ultrasound courtesy of Laurie Barber, MD). right eye was normal. The left eye had light perception vision, 360° perilimbal injection, mid-dilated pu- A B pil, and dull red reflex. There were no signs of penetrating injury. The angle was closed with an intraocular pressure of 61 mm Hg. A toxi- cology screen test result was positive for amphetamine. An initial diagnosis of angle-closure glaucoma led to initiation of timolol ma- leate, brimonidine tartrate, acetazol- amide, and isosorbide dinitrate therapy that reduced the intraocular pressure to 40 mm Hg. On the evening of admission, ocular ultra- sonography revealed thickening Figure 2. Axial (A) and coronal (B) computed tomographic scans show lens subluxation on day 2.

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©2000 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/25/2021 to the episode the patient had been Corresponding author: Chris- nal blade to penetrate the arterial observed injecting drugs into the topher T. Westfall, MD, Department of wall at the central bifurcation of the periocular tissues. Ophthalmology, University of Arkan- retinal artery (Figure 1). No no- sas for Medical Sciences, 4301 W table hemorrhage was noted. A 50- Comment. To our knowledge, this MarkhamSt,MailSlot#523,LittleRock, gauge flexible stylet made of nickel is the first reported case of endoph- AR 72205 (e-mail: westfallchristopher titanium was extended from a 19- thalmitis secondary to presumed il- @exchange.uams.edu). gauge support shaft and used to licit periorbital drug injection and cannulate the CRA through the ar- 1. Okada AA, D’Amico DJ. Endogenous endoph- the first reported case of lens dislo- thalmitis. In: Albert DM, Jakobiec FA, eds. Prin- teriotomy site. Cannulation was con- cation associated with B cereus en- ciples and Practice of Clinical Ophthalmology. Vol firmed by the ease of passage of the dophthalmitis. Unreliable patient 5. Philadelphia, Pa: WB Saunders Co; 1994: 3120-3126, 3379-3380. stylet into the CRA. Approximately history delayed correct diagnosis and 2. Beecher DJ, Pulido JS, Barney NP, Wong AC. Ex- 3.5 mm of the stylet entered the contributed to a poor outcome, but tracellular virulence factors in Bacillus cereus en- CRA. The stylet was moved using retrospective review of the initial dophthalmitis: methods and implication of in- volvement of hemolysin BL. Infect Immun. 1995; forward, backward, and circular mo- signs and symptoms and subse- 63:632-639. tions, and then withdrawn. A small quent eyewitness reports led us to 3. Ullman S, Pflugfelder SC, Hughes R, Forster RK. amount of semiclotted blood Bacillus cereus panophthalmitis manifesting as suspect orbital injection. Inadvert- an orbital cellulitis. Am J Ophthalmol. 1987;103: emerged from the arteriotomy site. ent ocular penetration and intraocu- 105-106. The caliber of the superior retinal lar injection may have caused acute arteries increased partially after angle closure at the patient’s initial cannulation; however, the inferior visit. Periocular injection or direct retinal arteries remained severely inoculation of the vitreous body with narrowed. Because it was unclear a dirty needle in turn progressed to Vitreous Surgery how the procedure might affect the B cereus endophthalmitis that for Central Retinal risk of ocular neovascularization, pe- rapidly led to lens dislocation. Al- Artery Occlusion ripheral endophotocoagulation was though other mechanisms may re- performed prophylactically to mini- sult in endophthalmitis, the lack of Central retinal artery (CRA) mize the risk. systemic sepsis, other infectious occlusion is a devastating disease Postoperatively, the patient was sources, or obvious trauma near the for which conventional therapies given oral aspirin, 325 mg daily. Ex- globe make these etiologies less are often relatively ineffective.1 amination findings on day 2 showed probable. Our report emphasizes the Since CRA occlusion is usually a visual acuity of counting fingers at virulent nature of B cereus, which caused by a physical obstruction 1.8 m. The appearance of the reti- typically causes retinal necrosis and in the CRA, we propose a mechani- nal vessels had not changed signifi- retinal detachment1,2 due to the pro- cal means of relieving the obstruc- cantly since the procedure. By the duction of multiple toxins and en- tion. We postulate that cannula- next examination on day 10, the cali- zymes.2 The orbit should be recog- tion of the CRA with a stylet during ber of the retinal vessels had re- nized as a potential site for illicit drug vitreous surgery may disrupt the turned to normal (Figure 2). An- injection, a practice which carries the obstructive agent and restore blood giographic images revealed a normal risk of inadvertent intraocular in- flow.2 retinal circulation time. The latest oculation. Our report illustrates 3 follow-up examination findings at 4 important aspects of B cereus en- Report of a Case. A 68-year-old months showed a corrected visual dophthalmitis: (1) A high index of man with diabetes developed CRA acuity of 20/25 OS. The cherry-red suspicion is necessary for early de- occlusion in his left eye. On initial spot had disappeared. A laboratory tection; (2) B cereus must be con- examination, his best-corrected vi- evaluation revealed an atheroma- sidered in an individual who abuses sual acuity was counting fingers at tous plaque in the thoracic aorta. drugs; and (3) The rapid destruc- 0.5 m OS. Funduscopy revealed a tion caused by this highly virulent cherry red spot and severely nar- Comment. Cannulation of the CRA organism in endophthalmitis may rowed retinal arteries. At approxi- is a novel surgical approach that al- result in lens subluxation. mately 30 hours after the onset of lows direct mechanical access to the vision loss, conventional treat- site of obstruction. This method pre- Douglas M. Blackmon, BA ments had still resulted in no im- sents the advantage of avoiding the Harold M. Calvert, MD provement in vision. The patient risk of neurological complications Paul M. Henry, MD declined the option of selective associated with selective thromboly- Christopher T. Westfall, MD thrombolysis. The option of vitrec- sis.2-4 In this case, immediate im- Little Rock, Ark tomy with vessel cannulation and provement in blood flow was mod- thrombus disruption under local an- est. It seemed that the thrombus was esthesia was then offered. The pa- only partially disrupted. In the fu- We would like to acknowledge the con- tient understood the experimental ture, to relieve the obstruction more tributions of Rebecca Martin, MD, and nature of this treatment and gave his completely, one might consider us- the Infectious Disease Department at informed consent. ing a longer stylet or an infusion can- the University of Arkansas for Medi- After vitrectomy, one of us nula to deliver thrombolytic agents cal Sciences. (W.M.T.) used a microvitreoreti- into the CRA. The excellent recov-

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Support Shaft

Stylet

Arteriotomy Site

Figure 1. Intraoperative digitized photographs. A, An arteriotomy is made over the optic nerve with a microvitreoretinal blade. B, The central retinal artery is cannulated with a stylet extended from a support shaft. C, Schematic explanation of the described cannulation.

Leber’s Hereditary Optic Neuropathy Masquerading as Retinal Vasculitis

Leber’s hereditary optic neuropathy (LHON) is a maternally inher- ited mitochondrial disease caused by several specific point mutations in mitochondrial DNA. The mutation at nucleotide position 11778 was the first point mutation to be identified and is the most common point mutation associated with LHON. For decades the diagnosis of LHON was dependent on the presence of clas- sic ophthalmoscopic findings of cir- cumpapillary telangiectatic micro- angiopathy, swelling of the nerve fiber layer around the disc (pseudo- Figure 2. Fundus photograph and fluorescein angiogram on postoperative day 10. The retinal vessels have regained normal caliber. A cherry-red spot is still visible. At the arteriotomy site, a tiny amount papilledema), and the absence of of fibrosis (arrow, A) and vascular dilatation (arrowhead, B) can be observed. leakage from the disc on fluorescein angiography. Genetic analysis allows characterization of the clini- ery of vision in this case suggests that Reprints: William M. Tang, MD, cal spectrum of LHON through the the restoration of blood flow may Department of Ophthalmology, Bos- identification of cases that in the past lead to functional improvement. ton University, 715 Albany St, Bos- would have remained undiag- ton, MA 02118-2526 (e-mail: nosed. We report a new finding of William M. Tang, MD [email protected]). peripheral retinal phlebitis associ- Trexler M. Topping, MD ated with the 11778 mutation in Boston, Mass 1. Atebara NH, Brown GC, Cater J. Efficacy of an- LHON. terior chamber paracentesis and Carbogen in treat- We do not have any commercial or ing acute nonarteritic central retinal artery oc- Report of a Case. A 17-year-old Af- clusion. Ophthalmology. 1995;102:2029-2034. proprietary interest in any product or 2. Tang WM, Han DP. A study of surgical ap- rican American woman with high- instrument discussed in this article. proaches to retinal vascular occlusions. Arch myopia was examined for a 5-month Ophthalmol. 2000;118:138-143. We thank Janice M. Burke, PhD, 3. Hayreh SS. Retinal arterial occlusion with LIF us- history of gradually declining vi- for providing eyebank tissue for labo- ing rTPA. Ophthalmology. 1999;106:1236-1238. sion in both eyes. There was no his- ratory testing with the support of core 4. Richard G, Lerche R-C, Knospe V, Zeumer H. tory of multiple sclerosis or LHON Treatment of retinal arterial occlusion with grant P30 EY01931 from the Na- local fibrinolysis using rTPA. Ophthalmology. in family members. Visual acuity was tional Eye Institute, Bethesda, Md. 1999;106:768-773. 20/100 OD and 20/400 OS. There

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Figure 1. A, Tilted, dysplastic optic nerve. B, Optic nerve temporal pallor.

sive visual loss and severe frontal lobe headaches. Visual acuity was now 2/200 OD with light perception OS. Ocular examination and fluorescein angiography were unchanged. Mag- netic resonance images of the brain and lumbar puncture were unremarkable with no evidence of multiple sclerosis. Molecular genetic analysis for known LHON mutations was positive for the 11778 mutation. The patient was treated with coenzyme Q supplementation (300 mg/d) for 6 months but her vision failed to im- prove in either eye. The patient has not developed clinically positive multiple sclerosis.

Figure 2. Old, inactive retinal phlebitis as seen in the periphery of both eyes. Comment. Leber’s hereditary optic neuropathy may masquerade as to- was a left relative afferent pupillary in the retinal periphery of either bacco-alcohol amblyopia1 or Star- defect and dyschromatopsia de- eye. A fluorescein angiogram of gardt’s maculopathy.2 The 11778 tected by Ishihara color plate test- both eyes appeared normal with no mutation has been associated with ing in each eye. Slitlamp examina- retinal vascular leakage or staining. a demyelinating neurological con- tion results from both eyes were The results of diagnostic labo- dition indistinguishable from mul- unremarkable. There were trace vit- ratory tests, including a chest x-ray, tiple sclerosis.3 The findings from reous cells in both eyes and vitre- VDRL test, fluorescent treponemal our examination of this patient, in- ous inflammatory condensates lo- antibody absorption test, sickle cell cluding vitritis, vasculitis, and op- cated inferiorly in the left eye, but test, tests of purified protein deriva- tic neuritis are commonly seen in pa- no pars plana snowbanks were ob- tive (tuberculin), angiotensin-con- tients with multiple sclerosis4 or served in either eye. Goldmann vi- verting enzyme, lysozyme, Lyme multiple sclerosis–like syndromes sual field testing showed bilateral antibodies, and serum electropho- such as pars planitis,5 further sup- central scotomas. Funduscopic resis, were unremarkable. Also un- porting an association between mul- examination revealed a right- remarkable were test results for an- tiple sclerosis and LHON mutation tilted, dysplastic optic nerve and tithrombin III, prothrombin time, 11178. These patients may be at high left optic nerve temporal pallor activated partial thromboplastin risk of developing multiple sclero- (Figure 1). The clinical maculae of time, protein C, protein S, protein sis years after the ocular findings are both eyes were unremarkable. The C resistance, antinuclear antibody, identified. retinal periphery of both eyes re- antiphospholipid antibodies, anti- This case extends the clinical vealed inactive vasculitis with vas- cardiolipin antibodies, antineutro- spectrum of LHON and does not in- cular sheathing of the retinal veins phil cytoplasmic antibody, and dicate a coincidental occurrence of (Figure 2), but no evidence of vaso- hepatitis B surface antigen. some other retinal inflammatory pro- occlusion. There was no arteriove- The patient was given predni- cess with the mitochondrial muta- nous shunting, retinal neovascular- sone (60 mg/d) but failed to return tion 11778. A complete systemic ization, or intraretinal hemorrhage until 2 months later with progres- evaluation for vasculitis, hyperco-

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©2000 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/25/2021 agulable states, collagen vascular Corresponding author: Eric S. Mann, with the 15257 mitochondrial DNA mutation. Arch Ophthalmol. 1993;111:1495-1499. disease, and infection was unreveal- MD, PhD, Saint Louis University 3. Harding AE, Sweeney MG, Miller DH, et al. Oc- ing. This report lends support to the Eye Institute, 1755 S Grand Blvd, St currence of multiple sclerosis–like illness in theory that LHON is a neuroreti- Louis, MO 63104 (e-mail: manne4 women who have Leber’s hereditary optic neuropathy mitochondrial DNA mutation. Brain. nopathy with a broad spectrum of @slu.edu). 1992;115:979-989. genotype-specific phenotypes. 4. Kerrison JB, Flynn T, Green WR. Retinal patho- logic changes in multiple sclerosis. Retina. 1994; Eric S. Mann, MD, PhD 1. Cullom ME, Heher KL, Miller NR, Savino PJ, 14:445-451. Suzanne P. Handler, MD Johns DR. Leber’s hereditary optic neuropathy 5. Malinowski SM, Pulido JS, Goeken NE, Brown masquerading as a tobacco-alcohol amblyopia. CK, Folk JC. The association of HLA-B8, B51, Sophia M. Chung, MD Arch Ophthalmol. 1993;111:1482-1485. DR2, and multiple sclerosis in pars planitis. Oph- St Louis, Mo 2. Heher KL, Johns DR. Maculopathy associated thalmology. 1993;100:1199-1205.

Ophthalmological Numismatics

A look at the past...

lbrecht von Graefe, 1829-1870, the renowned ophthalmologist of Berlin and son of Carl F. von Graefe, is honored by the Ophthalmological Society of Heidelberg by being portrayed on its award medal, which is presented every 10 Ayears. This, the first piece that was awarded in 1886, was presented to von Helmholtz. Von Graefe was among the first to use the newly invented ophthalmoscope of von Helmholtz. He announced a cure for acute glaucoma by surgical iri- dectomy and improved techniques for cataract and strabismus surgery. He is also the founder of the journal Archiv Fur Oph- thalmologie. This medal was engraved by E. Weigang and F. Hartzer. The obverse (Figure 1) depicts von Graefe’s bust fac- ing right surrounded by an inscription. The reverse (Figure 2) depicts an inscription surrounded by a wreath with an inscription above. The original prize medal is struck in gold. Bronze copies were also made.

Courtesy of: Jay M. Galst, MD, 30 E 60th St, New York, NY 10022.

Figure 1. Figure 2.

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