CASE REPORTS AND SMALL CASE SERIES

Can an Eye in Phthisis Be Rehabilitated? A Case of Improved Vision With 1-Year Follow-up

hthisis bulbi implies, in clini- cal terminology, a shrunken , usually from ceased Figure 1. The patient suffered a severe alkali Figure 2. The right eye seemed collapsed and P burn 9 months prior to surgery. Visual acuity the intraocular pressure was extremely soft by aqueous humor formation (phthi- was light perception OU. palpation. The distance from the corneal back sis meaning “wasting away”). The in- surface to the was 15.5 mm. traocular pressure approaches 0 mm Hg. As a consequence, the be- ineffective, since the source of nu- We tried keratoprosthesis, pre- comes distorted and can develop trition, a healthy flow of aqueous, is ceded by a buccal mucosal graft that and scarring, and the de- absent. With the advent of more ad- was carried out by Jeffrey Green, MD. velops . Both seem to oc- vanced techniques for keratopros- The keratoprosthesis surgery was cur due to the lack of nutrition by thesis surgery and more long-term, done 2 months later, using a Dohl- the aqueous. In addition, edema can postoperative stability, there may be man-Doane type II device (Massa- develop in the macula and the op- new hope for eyes going into phthi- chusetts Eye and Ear Infimary, Bos- tic nerve head and vision suffers ac- sis.2 Initial attempts in this direc- ton).4 It was inserted into a 9.5-mm cordingly. Finally, cyclitic mem- tion have been made in the past, but corneal graft from a frozen-stored do- branes and proliferative vitreal there was no success in restoring vi- nor eye in a previously described can develop, resulting in sion.3 In this report, we describe a manner.5 After taking down the buc- total and scar for- patient with a chemical burn that led cal mucosal graft to bare the cornea, mation. The cause of phthisis is of- to a shrunken eye, no palpable in- the intraocular pressure was again ten , either long-term or fol- traocular pressure, an opaque cor- evaluated by indentation and it lowing trauma, surgery, or end- nea (due in part to the direct effect seemed to be 0 mm Hg. The eye was stage, heavily treated . of the alkali), and an attached retina, opened with a 9.0-mm trephine and Treatment of phthisis is gener- who regained substantial vision fol- the lens remnants were excised. The ally considered hopeless. Aggressive lowing keratoprosthesis surgery and was totally scarred and treatment of intraocular inflammation was followed up for 1 year. atrophic. The and macula in uveitis or avoiding too much cy- were inspected with an endoscope clodestructioninglaucomaduringthe Report of a Case. The patient, a citi- and a moderate vitrectomy was car- early stage with hypotony may delay zen of Ghana, had alkali thrown in ried out. The graft-prosthesis combi- or prevent the final collapse. In some his face 9 months prior to the refer- nation was then placed in the open- rare instances of chronic cyclodialy- ral. The burn was extremely severe ing and secured with sixteen 9-0 sisorseverecycliticmembranes,asur- (Figure 1). Ophthalmic examina- nylon sutures. A scleral patch with a gical approach has been reported to tion in April 1997 showed both eyes central hole was threaded over the beofsomevalue.1 Ingeneral,however, to be totally soft and collapsed. In the nub of the prosthesis for reinforce- if the intraocular pressure is close to right eye, the upper margin was ment, followed by reattachment of the 0, the eye is collapsed, the cornea is fused to the lower part of the cornea hinged buccal mucosa so that it fully edematous, the lens is cataractous, the (Figure 2). Visual acuity was light covered the cornea. Eight milli- ocularvolumeisreducedtohalforone perception only, with reasonably ac- grams of dexamethasone sodium third of the normal volume, and the curate projection. B-scan ultrasonog- phosphate was injected through the ocular layers are correspondingly raphy showed that the retina and cho- lower eyelid. thickened, no treatment has, to our roid were attached and the vitreous Postoperatively, the mucosa knowledge, been effective in restor- cavity contained some low reflective overlying the keratoprosthesis broke ing vision. debris and probably posterior vitre- up within 1 week (the goal is com- Any proposed treatment of ous detachment. An A-scan ultra- plete coverage for 2 months); how- phthisis must be surgical, if for no sonogram showed a 15.5-mm dis- ever, later tissue retraction around other reason than to restore the clar- tance between the posterior surface the prosthesis nub was minimal. ity of the cornea. In this respect, of the cornea and the anterior sur- Topical medication consisting of 1% standard corneal transplantation is face of the retina. medroxyprogesterone acetate sus-

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©1999 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 generalized disorganization of the in- eryl methacrylate, has been interest- traocular contents.6 In our case, the ing in this regard.7 This hydrogel was standard clinical definition of phthi- tested for lack of toxic reaction in the sis will be used—referring to to irre- vitreous8 and in the cornea.9 It was versible cessation of the aqueous hu- also found that a dried pellet of this mor formation, near 0 mm Hg material placed in the eye of an ani- intraocular pressure, and a shrunken mal could swell up, replace the vit- eye, without consideration of the sta- reous, and exert a desired intraocu- tus of the retina or other intraocular lar pressure.3 Our clinical experience Figure 3. Appearance after buccal mucosal structures. with this hydrogel has so far been dis- graft, followed up 2 months later by Our patient had the clinical ap- appointing, however, because the hy- keratoprosthesis and vitrectomy. Visual acuity was 20/60 after a 1-year follow-up. pearance of a phthisical eye: no de- drogel seems to be easily impreg- tectable intraocular pressure, the nated by proteins that render it bulb collapsed to a much reduced opaque. Silicone oil can be used pension (to discourage tissue necro- axial length, a swollen and opaque (D. R. C. Caldwell, MD, oral com- sis and melt) and an antibiotic was cornea, and a ciliary body that munication, November, 1994), which given 4 times daily, reduced to 2 looked totally atrophic on ophthal- is optically clear, but does not exert times daily after 6 months.2 One mic examination. No retinal detach- a swelling pressure and is difficult to month postoperatively, the ante- ment had occurred and there was no handle. Prevention or treatment of rior chamber hardly exhibited any obvious (the optic retinal detachment in phthisical eyes inflammatory reaction, only a rare nerve could not be well evaluated). will clearly be the next frontier. cell; however, 40 mg of triamcino- The lack of macular edema might be Our patient is, to our knowl- lone was injected once through the attributable to a low residual, non- edge, the first report of a phthisical eye lower eyelid. detectable, intraocular pressure. Pal- with severely opaque cornea who had Visual acuity was 20/100 OU pation is a crude way of estimating substantial vision restored—at least 1 week after the operation and the intraocular pressure but the only during this short follow-up period. gradually rose to 20/60 OU during one available with this type of kera- the ensuing 5 months (Figure 3). toprosthesis. Claes H. Dohlman, MD, PhD This required a spectacle correc- In general, phthisis seems to Donald J. D’Amico, MD tion of +10.00 diopters (D) due to a initially affect the cornea and the Boston, Mass miscalculation in the choosing of lens. Removal of a cataractous lens the prosthesis. The optic disc was constitutes no particular clinical This study was funded by Saad A. A. difficult to see due to an overhang- problem, but restoring corneal trans- Al-Rashed, Safat, Kuwait. ing vitreous veil, but the macula was parency is a more formidable chal- Corresponding author: Claes H. without edema and showed no ab- lenge since standard transplanta- Dohlman, MD, PhD, Department of normalities. The visual field showed tion is impossible. Technique and , Massachusetts Eye an enlarged blind spot and a sug- follow-up regimens for keratopros- and Ear Infirmary, Harvard Medical gestion of a nasal step, most likely thesis, however, have developed to School, 243 Charles St, Boston, MA due to a short period of high pres- a level where it seems reasonable to 02114. sure soon after the burn. One year try it even in a phthisical situation. after the keratoprosthesis surgery the The follow-up time of our case is 1. Zarbin MA, Michels RG, Green WR. Dissection of epiciliary tissue to treat chronic hypotony af- situation seems stable. short (only 1 year), and long-term ter surgery for retinal detachment with prolif- problems may still occur, as in many erative vitreo-retinopathy. Retina. 1991;11:208- Comment. The definition of ocular other keratoprosthesis cases. Still, 213. 2. Dohlman CH. Keratoprosthesis. In: Krachmer J, phthisis is vague. Severe hypotony our study does show that some vi- Mannis M, Holland E, eds. Cornea. Vol 3. St due to overfiltration after glaucoma sion can be restored, at least tem- Louis, Mo: Mosby–Year Book Inc; 1997:1855- procedures or extensive traumatic cy- porarily, in an eye with close to 1863. 3. Dohlman CH, Refojo MF, Webster RG, Pfister clodialysis is usually not labeled as 0 mm Hg intraocular pressure and RR, Doane MG. Tension intraoculaire sans corps phthisis. In such situations, the aque- an intraocular volume reduced to ciliaire. Arch Ophtalmol Rev Gen Ophtamol. 1969; 29:849-854. ous formation is grossly intact and less than half that of a normal eye. 4. Doane MG, Dohlman CH, Bearse G. Fabrication therefore provides adequate nutri- Retinal detachment is a com- of a keratoprosthesis. Cornea. 1996;15:179-184. tion to the cornea and the lens is pro- mon end point in phthisical eyes, es- 5. Dohlman CH, Waller SG, Netland PA. Kerato- prosthesis surgery. In: Lindquist T, Lindstrom vided, keeping these tissues transpar- pecially when chronic intraocular in- R, eds. Ophthalmic Surgery Update #4. St Louis, ent. If, on the other hand, the ciliary flammation is prominent. In such Mo: Mosby–Year Book Inc; 1997:1-32. body is destroyed and the aqueous se- cases, a keratoprosthesis has to be 6. Hogan M, Zimmerman L. Ophthalmic Pathol- ogy. Philadelphia, Pa: WB Saunders Co; 1962. cretion has ceased, the damage is per- combined with methods to splint or 7. Refojo MF. Glyceryl methacrylate hydrogels. manent and the cornea and the lens reattach the retina—obviously a for- J Appl Polymer Sci. 1965;9:3161-3170. 8. Daniele S, Refojo MF, Schepens CL, Freeman suffer accordingly. This state is la- midable task. Filling the vitreous cav- HM. Glyceryl methacrylate hydrogel as a vitre- beled by most clinicians as “phthi- ity with a clear substance that exerts ous implant: an experimental study. Arch Oph- sis.” Some ophthalmic pathologists a mild, mechanical pressure out- thalmol. 1968;80:120-127. 9. Dohlman CH, Refojo MF, Rose J. Synthetic poly- further restrict the term phthisis to de- ward may be a future possibility. The mers in corneal surgery, I: glyceral methacry- scribe shrunken eyes that also show synthesis of a clear hydrogel, glyc- late. Arch Ophthalmol. 1967;77:252-257.

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©1999 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 of external beam irradiation in years. A fluorescein angiogram per- Good Visual Outcome November 1992 (dose fraction, 1.8 formed 47 months after develop- Following Laser Therapy Gy; 25 treatments in 36 days). Sev- ment of proliferative radiation reti- for Proliferative Radiation enteen months later an examina- nopathy demonstrated intact foveal Retinopathy tion revealed visual acuities of capillaries and no retinovascular 20/25 OD and 20/40 OS, nonprolif- leakage in the left eye. Early prolif- Radiation retinopathy is a poten- erative radiation retinopathy in the erative radiation retinopathy was tially severe complication of radia- right eye, and neovascularization present in the right eye. tion therapy for orbital disease. with vitreous hemorrhage and clini- Findings range from intraretinal cally significant macular edema con- Comment. Head and neck irradia- hemorrhages, cotton-wool spots, and firmed by contact lens examination tion can cause ophthalmic compli- macular edema (nonproliferative ra- in the left eye. Fluorescein angio- cations including cataracts, optic diation retinopathy) to extensive gram of the left eye demonstrated se- neuropathy, and radiation retinopa- retinal capillary ischemia leading to vere capillary nonperfusion and dif- thy.1 Radiation retinopathy has been neovascularization and vitreous fuse cystoid macular edema reported in radiation doses as low as hemorrhage (proliferative radia- (Figure 1, A and B). The patient re- 11 Gy, but is infrequent below the tion retinopathy). Kinyoun et al1 re- ceived grid laser treatment and pan- dose of 45 Gy.2,3 Our patient re- ported that eyes with proliferative ra- retinal photocoagulation in the left ceived 45 Gy of irradiation. While diation retinopathy had poor visual eye (Figure 1, C). He required a pars visual prognosis in patients receiv- prognosis despite treatment with plana vitrectomy for nonclearing vit- ing laser therapy for radiation- panretinal photocoagulation. We re- reous hemorrhage. Visual acuity im- induced macular edema is favor- port a case of a man with prolifera- proved to 20/25 OU with resolu- able, poor visual outcome is reported tive radiation retinopathy treated tion of the macular edema and for patients treated for proliferative with laser therapy who retained ex- vitreous hemorrhage. The patient radiation retinopathy, presumably cellent vision for 5 years. has had no recurrence of prolifera- due to severe capillary nonperfu- tive radiation retinopathy or macu- sion and ischemia of the macula.4 Report of a Case. A 39-year-old lar edema in the left eye (Figure 2), Kinyoun et al1 documented that man with a history of pineoblas- and his visual acuity after panretinal photocoagulation halted toma had decreased vision in his extraction 1 year later has re- new vessel formation in eyes with left eye. The patient received 45 Gy mained stable at 20/20 OU for 3 proliferative radiation retinopathy;

A B C

Figure 1. A, Venous phase fluorescein angiogram of the left eye demonstrating extensive capillary nonperfusion. B, Late-phase angiogram of same eye shows diffuse macular edema. C, Color fundus photograph of the same eye after grid and panretinal photocoagulation laser treatment showing vitreous hemorrhage.

A B C

Figure 2. A, Venous phase fluorescein angiogram of the left eye 5 years after first visit with proliferative radiation retinopathy. B, Perifoveal capillaries are patent and macular edema is not evident in the late phase of the angiogram. C, Color fundus photograph of the left eye at 5-year follow-up showing grid and panretinal photocoagulation laser and without evidence of active proliferative radiation retinopathy or macular edema.

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©1999 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 however, 86% of patients devel- 3. Parsons JT, Bova FJ, Fitzgerald CR, Menden- wear in both eyes for 1 year. Her hall WM, Million RR. Radiation retinopathy af- oped visual acuities less than 20/ ter external-beam irradiation: analysis of time- medical history was unremarkable. 200 OU and no eyes had visual acu- dose factors. Int J Radiat Oncol Biol Phys. 1994; Best-corrected visual acuity was ity better than 20/50 OU after a mean 30:765-773. 20/20 OU. Slitlamp examination 4. Kinyoun JL, Zamber RW, Lawrence BS, Barlow follow-up time of 75 months. WE, Arnold AM. Photocoagulation treatment for showed the presence of coarse Ninety-three percent of their pa- clinically significant radiation macular oe- irregular epithelium plaques origi- tients with proliferative radiation dema. Br J Ophthalmol. 1995;79:144-149. nating from the superior aspect of retinopathy also had optic neuropa- the limbus in both eyes into the thy, 86% had macular edema, and superior aspect of the cornea 100% had macular ischemia.1 Our A Confocal Microscopic (Figure 1). At the subepithelial patient, who had no signs of optic Study of Advancing level, a diffuse haze was noted. The neuropathy, had regression of neo- Wavelike Epitheliopathy remainder of the ophthalmic vascularization, resolution of macu- examination, including examina- lar edema and capillary nonperfu- Advancing wavelike epitheliopa- tion of the , showed no sion, and restoration of a visual acuity thy was first described by D’Aversa abnormalities. The patient was of 20/20 OU after laser therapy. et al1 In their study, 11 eyes of 7 pa- examined using a prototype, white- We agree that patients receiv- tients were seen with well-demar- light, tandem scanning, confocal ing head and neck irradiation need cated, centripetally advancing waves microscope (LSU Eye Center, New to be screened for radiation reti- of irregular epithelium and subepi- Orleans, La) using a ϫ24/0.60 con- nopathy. However, it is possible that thelial haze, originating from the up- tact objective (Tandem Scanning proliferative radiation retinopathy it- per aspect of the limbus. Identified Corp, Reston, Va). Ophthalmic self does not confer a poor visual risk factors included the use of topi- examination was performed with prognosis if other irreversible forms cal antiglaucoma medications or liquefied hydroxypropyl methylcel- of vision loss such as optic neuropa- contact lens care solutions, contact lulose as a coupling gel. Confocal thy and macular ischemia are not lens wear, past ocular surgery, acne microscopy showed the presence present. Indeed, early detection of rosacea, and atopic dermatitis. The of atypical, elongated, and centrip- proliferative radiation retinopathy condition was reported to respond etally oriented cells with easily rec- and treatment with laser may im- to 1% silver nitrate applied to the su- ognizable nuclei at the level of the prove visual acuity. perior aspect of the limbus. To our abnormal epithelium in both eyes knowledge, no other cases have been (Figure 2, left). At the subepithe- Jennifer E. Thorne, MD documented. We describe a patient lial level, confluent hyperreflective Albert M. Maguire, MD with advancing wavelike epitheli- images were detected (Figure 2, Philadelphia, Pa opathy and the confocal micro- right). The areas adjacent to the scopic findings. plaques of irregular epithelium Corresponding author: Albert M. showed no abnormalities. The Maguire, MD, Scheie Eye Institute, 51 Report of a Case. A 49-year-old patient was treated with 1% silver N 39th St, Philadelphia, PA 19104. white woman was referred for nitrate applied to the superior

1. Kinyoun JL, Lawrence BS, Barlow WE. Prolif- evaluation of corneal abnormali- aspect of the limbus. Subsequently, erative radiation retinopathy. Arch Ophthalmol. ties. Her chief complaint was ocu- the symptoms subsided rapidly 1996;114:1097-1100. lar discomfort and in and complete resolution was noted 2. Maguire AM, Schachat AP. Radiation retinopa- thy. In: Ryan J, Stephen R, eds. Retina. St Louis, both eyes for 1 month, and she had clinically 1 month after the treat- Mo: CV Mosby Co; 1989:1509-1514. a history of daily soft contact lens ment. Few abnormal epithelial

Figure 1. In the superior cornea, plaques of coarse irregular epithelium revealed by fluorescein staining were seen in the both eyes. They were more notable in the left eye and seemed to originate from the upper aspect of the limbus. A faint subepithelial haze was also present.

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©1999 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 Figure 2. Left, In both eyes, confocal microscopy revealed the presence of atypical elongated cells with centripetally oriented, long-axis, and hyperreflective nuclei. Right, At the subepithelial level, confluent hyperreflective images were found (original magnification ϫ210).

cells could still be demonstrated at cornea and may allow diagnosis of the limbus in both eyes by confocal advancing wavelike epitheliopathy Traumatic Enucleation From microscopy; however, the patient by demonstrating the atypical elon- a High-Pressure Water Jet remained asymptomatic during the gated cells. following 6 months and further treatment was not necessary. Auguste G.-Y. Chiou, MD This article describes an unusual Stephen C. Kaufman, MD, PhD case of enucleation from a high- Comment. The clinical presenta- Roger W. Beuerman, PhD pressure water jet. Treatment is de- tion of our patient is similar to that Toshihiko Ohta, MD scribed and an etiologic hypothesis described by D’Aversa et al1 and Herbert E. Kaufman, MD is presented. could be easily differentiated from New Orleans, La superior limbic keratoconjunctivi- Report of a Case. A 37-year-old man tis and corneal pannus. Rapid re- This study was supported in part by was seen in the emergency depart- sponse to 1% silver nitrate made the Public Health Service grants EY00346 ment with a traumatic injury to his possibility of corneal epithelial dys- (Dr S. Kaufman) and EY02580 and right . The patient, not wearing plasia or carcinoma very unlikely. EY02377 (Dr H Kaufman), from the protective eyewear, was tightening a D’Aversa et al postulated that National Eye Institute, National In- high-pressure industrial pipe that be- abnormal limbal cells proliferate and stitutes of Health, Bethesda, Md; De- gan to leak. Owing to a sudden mal- migrate to the cornea. They dis- partment of the Army, Cooperative function, a high-pressure water jet closed parakeratotic alterations and Agreement DAMD17-93-V-3013 (this was directed into his right orbit. The underlying mononuclear cell infil- does not necessarily reflect the posi- right globe was found approxi- tration in the limbal conjunctiva; tion or the policy of the government, mately 45 m (50 yd) from the scene however, they did not demonstrate and no official endorsement should be of the injury by emergency person- cytological alterations in the cor- inferred) (Drs Beuerman and H. Kauf- nel. Ophthalmic examination of the neal epithelium. Using the confo- man); an unrestricted departmental right orbit showed relatively clean, cal microscope, we could identify the grant from Research to Prevent Blind- soft tissue with conjunctival chemo- presence of highly atypical cells at ness Inc, New York, NY (Dr Chiou); sis and an anophthalmic socket. Gross the level of the epithelium. The sub- and grants from the Socie´te´ Acade´mi- and histopathologic examination find- epithelial hyperreflective layer prob- que Vaudoise (Dr Chiou); the Swiss ings of the eye revealed an intact globe ably corresponds to the hazy struc- National Research Foundation (Dr with no readily identifiable sites of ture seen on slitlamp examination Chiou); and the Verrey Foundation scleral rupture and 15 mm of optic and is compatible with fibrous tis- (Dr Chiou) Lausanne, Switzerland. nerve present (Figure 1). The ex- sue. Further studies are necessary to The authors do not have any traocular muscles were avulsed investigate its exact composition. commercial or proprietary interest in through their insertions on the globe. Our case supports the exist- the products or companies cited in this A computed tomographic scan of the ence of the clinical entity described article and do not have any financial orbits confirmed the anophthalmic 1 by D’Aversa et al and endorses that interest or receive payment as a con- socket. The were their treatment with silver nitrate sultant, reviewer, or evaluator. in their normal anatomical positions may be clinically effective. Confo- Reprints: Roger Beuerman, PhD, and intact (Figure 2). Ophthalmic cal microscopic findings of remain- LSU Eye Center, 2020 Gravier St, examination of the left eye, includ- ing abnormal epithelial cells after the Suite B, New Orleans, LA 70112- ing confrontation visual fields, treatment may account for the need 2234 (e-mail: [email protected]). showed no abnormalities. of repeated treatments in some pa- The patient underwent right tients, as described by D’Aversa et al. 1. D’Aversa G, Luchs JL, Fox MJ, Rosenbaum PS, socket and orbital debridement and Udell IJ. Advancing wave-like epitheliopathy: Confocal microscopy enables non- clinical features and treatment. Ophthalmology. a moderate amount of ecchymotic invasive in vivo examination of the 1997;104:962-969. nonviable tissue was removed. The

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©1999 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 tion injuries to the hand. J Trauma. 1991;31: 110. 3. Holds JB, Patrinely JR, Zimmerman PL, Ander- son RL. Hydraulic orbital injection injuries. Oph- thalmology. 1993;100;1475-1482. 4. Krauss HR, Yee RD, Foos RY. Autoenucleation. Surv Ophthalmol. 1984;29:179-187.

A Hereditary Chiasmal

Figure 1. A gross specimen of the right globe. Rarely is a nonneoplastic disorder re- Note some debris on . The sponsible for a bitemporal visual remnant is seen with an intact sclera and cornea field defect, and in those cases, me- and extraocular muscle stumps present at insertion. chanical or radiation injury, inflam- mation, infection, demyelination, in- toxication, infarction, or hypoplasia orbit was explored extensively and of the optic chiasm are the mecha- the recti muscles were isolated. The nisms. We have encountered a fam- muscle ends were pulled anteriorly ily in which 3 siblings had a unique, and sutured to a 20-mm, scleral- presumably hereditary neuropathy wrapped, hydroxyapatite implant manifested by a chiasmatic visual through scleral fenestrations. field defect. Six months after the initial in- jury and surgery, the patient showed Report of Cases. The 3 white pa- excellentcosmeticresults,withawell- tients whose histories are presented healedrightorbitandexcellentsocket below represent all of the children of motility. Nuclear medicine imaging a nonconsanguineous marriage be- Figure 2. Coronal and axial computed revealedawell-vascularized,hydroxy- tomographic sections done the day of the initial tween a healthy mother of Puerto apatite implant. trauma, showing the anophthalmic right socket Rican descent and a healthy father of with an intact orbital rim. The optic nerve stump Irish descent. and extraocular muscle bellies show some Comment. Systemic high-pressure intraorbital air. Case 1. A healthy 28-year-old injection injuries have been docu- woman was advised to have an oph- mented in the literature since the thalmic examination because an ab- 1 1930s. Most of these have oc- nective tissue support, the 4 recti normality in her sister’s optic nerves curred in industrial settings and have near their insertions, and the optic had been discovered. The patient’s involved a variety of high-pressure nerve. Orbital trauma associated only eye problem had been fully cor- grease, air, and water machines that with anterior pressure alone usu- rectable and . 2 cause systemic trauma. These pipes ally results in . The Her neurological and endocrine his- contain water at pressures of be- pathologic condition in our patient tories showed no abnormalities and tween 6000 and 8000 psi, whereas is similar to that reported in psychi- an ophthalmologist found that her pressures of only 100 psi are neces- atric patients, where a finger or in- visual acuity was 20/20 OU, but she sary to penetrate skin. A break in the strument is placed behind the globe had pallor of her optic nerves and a closed system can propel water at and force is applied outward, result- bitemporal visual field defect. A speeds of up to 600 ft/s—close to the ing in enucleation.4 This is not a computed tomographic scan of the muzzle velocities of some rifles. common pathophysiological mecha- brain showed no abnormalities. She Similar injuries to the eyes and ad- nism of injury, but considering the remained asymptomatic and was re- nexa are much less common. Holds velocities attainable with pressur- ferred for evaluation at age 35 years. 3 et al described 8 patients with hy- ized fluids, one that should not be Her best-corrected visual acu- draulic orbital injection injuries. No surprising. ity was 20/15 OU. She missed sev- patient lost vision permanently as a eral of the Ishihara test plates with sequelae of the initial trauma. Dan D. DeAngelis, MD each eye, but she made no errors To our knowledge, this is the James H. Oestreicher, MD, FRCSC when tested with the Farnsworth first reported case of a hydraulic or- Toronto, Ontario D-15 panel. There was a bilateral su- bital injection injury resulting in perotemporal quadrantanopsia enucleation. The proposed mecha- Reprints: James H. Oestreicher, MD, (Figure 1). Her corneal nerves nism of injury in this patient in- FRCSC, 309-1033 Bay St, Toronto, seemed unusually prominent and volved a high-pressure jet of water Ontario, Canada, M5S 3A5. there were white dots scattered in the transecting the conjunctiva, travel- cortex of both lenses. Both optic ling to the retrobulbar space, and 1. Reese CE. Penetration of tissue by fuel oil un- discs were atrophic but of normal der high pressure from diesel engine. JAMA. then building up enough posterior 1937;109:866-867. size. Findings from the remainder of pressure to rupture all of the con- 2. Pai CH, Wei DC, Hou SP. High pressure injec- her examination showed no abnor-

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©1999 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 malities. Magnetic resonance imag- ing scan of the brain and orbits with gadolinium injection and full-field and foveal electroretinograms showed no abnormalities. Blood test results for 4 of the mitochondrial muta- tions known to be associated with 30° 30° Leber hereditary optic neuropathy (codons 11778, 14484, 15257, and 3468) were normal. Her condition re- mains unchanged 5 years later. Case 2. The older brother of pa- tient 1 was found to have abnormal optic nerves when he went to an op- Figure 1. Static automated visual fields from patient 1 show bilateral superotemporal defects respecting tometrist at age 27 years to have his the vertical and horizontal meridians. contact lenses checked. He was in good general health and his only eye problem had been myopia and astig- matism that was fully correctable with lenses. An ophthalmologist to whom he was referred found that his visual acuity was 20/20 OU with slight posterior subcapsular cata- racts and pale optic discs. Auto- 30° 30° mated perimetry showed defects near fixation. Findings from the neu- rological examination, 100-Hue color testing, magnetic resonance imaging scanning, and pattern vi- sual evoked response testing showed no abnormalities. He was exam- Figure 2. Static automated visual fields from patient 2 show bilateral superotemporal defects respecting ined again at age 33 years by a neuro- the vertical and horizontal meridians. ophthalmologist. Best-corrected vi- sual acuity was 20/20 OU. On kinetic visual field were noted dur- 2.5 of the 14 plates with her left. Slit- Ishihara color plate testing, he ing testing. Computed tomo- lamp examination showed no abnor- missed 2 with his right eye and 1 graphic scans showed no abnormali- malities. Humphrey visual fields re- with his left. Slitlamp examination ties at ages 27 and 30 years. At age vealed bilateral superotemporal field revealed mildly thickened corneal 32 years, Humphrey visual field test- defects (Figure 3). The mean de- nerves and posterior subcapsular ing showed superotemporal de- viation was unchanged compared cataracts in both eyes. There was no fects respecting the vertical merid- with the automated visual fields done relative afferent pupillary defect. ian. Magnetic resonance imaging at age 32 years. There was diffuse op- Humphrey visual field testing revealed a small, hyperintense, in- tic nerve pallor of both optic nerve showed central dropout with a su- trasellar lesion in the left side of the heads with temporal excavation. The perotemporal loss approaching the pituitary gland without suprasellar optic discs were normal sized. vertical meridian in each eye extension, presumed to be a pitu- The father's family history is no- (Figure 2). Both optic nerves were itary cyst. When examined by a table only for cataracts. The mother’s pale but of normal size. neuro-ophthalmologist at age 37 family history is notable for siblings Case 3. The younger sister of years, her visual acuity was 20/25 who died at ages 14 and 12 years of a patient 1 allegedly had poor vision OU. She correctly identified 2 of the neurologicaldiseasecharacterizedini- since childhood and a “lazy eye” that 14 Ishihara color test plates with tially by stuttering and loss of balance, was treated with exercises. Mi- each eye. There were bitemporal vi- progressing to bed confinement, and graine headaches had been present sual field defects on static visual field aphasia. Further details of their ill- since age 15 years. As early as age testing and both optic discs were nesses are unavailable. Both parents 27 years she was noted to have el- atrophic but of normal size. A sec- were free of systemic disease, had nor- evated prolactin levels but no endo- ond magnetic resonance imaging mal corrected visual acuities, Hum- crine symptoms. Ophthalmic ex- scan showed no abnormalities. phrey automated visual field results, amination then revealed a visual She was examined by a neuro- colorvision(Ishiharacolorplates),and acuity of 20/25 OD and 20/20 OS, 9 ophthalmologist 2 years later. Her optic nerve heads. Patient 1 has 2 of 14 Ishihara color plates correct best-corrected visual acuity was 20/25 daughters, a 12-year-old and a 9-year- with each eye; enlarged blind spots OD and 20/20 OS. On color vision old , both of whom are healthy. Both and loss of superotemporal visual testing, she correctly identified 3.5 of had neuro-ophthalmic examinations, field and bilateral optic atrophy on the 14 plates with her right eye and testing visual acuity, color vision, and

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©1999 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 tine examinations (without perim- etry) many years before discovery of the optic disc pallor, but it is pos- sible that the pallor was present but missed. None of the siblings has shown a decline in visual function 30° 30° under observation following discov- ery of the defect. In certain congen- ital optic neuropathies, the optic disc is hypoplastic. None of our pa- tients had discernible hypoplasia, but subtle degrees of hypoplasia can be hard to recognize. If acquired post- Figure 3. Static automated visual fields from patient 3 show bilateral superotemporal defects respecting natally, the latest the disorder could the vertical and horizontal meridians. have begun was in the third decade of life. visual fields, as well as visualization duced visual acuity in 1 eye and her Bitemporal visual field defects oftheopticnerves,allofwhichshowed bilateral dyschromatopsia imply that have been identified in hereditary no abnormalities. The older daughter she also has some involvement of optic neuropathies. Raaf and Bair1 of patient 1 had strabismic uncrossed axons. described the findings in patients that was successfully treated with It is highly unlikely that the dis- from a family with Leber heredi- patching. Patient 2 has an 18-month- order was not inherited as a men- tary optic neuropathy. Two sib- old son, who is healthy, and patient delian dominant trait since neither lings, both with impaired visual acu- 3 has a 9-year-old son and a 2-year- parent was affected. Only in the ity, had visual field defects with old daughter, both of whom are event that an affected man other than bitemporal characteristics. Weiner healthy. the putative father sired all 3 sib- et al2 reported a sporadic case of lings could this conclusion be con- Leber hereditary optic neuropathy Comment. We suspect that the 3 sib- founded. An illness involving an en- in a woman whose first symptom lings described in this article have tire sibship but sparing the parents was a temporal blur. On her initial a unique optic neuropathy that is could be genetically or nongeneti- examination she had reduced vi- manifested exclusively or predomi- cally inherited. Nongenetic, static, sual acuity in one eye but normal vi- nantly at the level of the optic chi- congenital optic neuropathies in sual acuity in the other with a bi- asm based on the presence of typi- multiple siblings can, albeit rarely, temporal visual field defect, densest cal chiasmatic visual field defects, result from an abnormal uterine en- adjacent to fixation. Manchester and and is probably inherited as an au- vironment. Segmental optic nerve Calhoun3 reported bitemporal vi- tosomal recessive trait. While we rec- hypoplasia in the offspring of moth- sual defects in several members of ognize that centrocecal can ers with diabetes mellitus is one of 2 generations of a family with domi- be mistaken for chiasmatic bitem- the few examples of this phenom- nantly inherited optic atrophy. Al- poral defects and that automated pe- enon; however, nongenetic inherit- though 2 of the patients were asymp- rimetry can give the false impres- ance of this kind cannot be ruled out tomatic, all of them had subnormal sion that a temporal defect comes to, in our cases. Mutations in mitochon- visual acuity. Votruba et al,4 in their but does not cross, the vertical mid- drial DNA can be transmitted extensive and intensive evaluation line, nevertheless we are confident through unaffected maternal carri- of patients with dominantly inher- that our patients’ defects were chi- ers as in Leber hereditary optic neu- ited optic atrophy, found that 33 of asmatic. Centrocecal defects would ropathy. Leber hereditary optic neu- 50 study patients had superotem- not give a defect confined to the su- ropathy was ruled out in patient 1 poral visual field defects when tested perior quadrant and would not be and, without special molecular in- with automated perimetry. It is im- likely to spare Snellen visual acu- vestigations and extensive informa- possible to determine if any them ities in every patient. The issue of the tion about multiple generations of were asymptomatic or had a pure midline boundary can be resolved in the family, this possibility cannot be chiasmatic syndrome. 2 of the patients because testing on evaluated. Autosomal recessive men- How might a congenital bitem- several occasions with Goldmann delian inheritance would be the poral visual field defect eventuate perimetry demonstrated that their vi- mechanism most likely to explain from a genetic disorder? Recent re- sual field defects “respected” the ver- the occurrence of the optic neuropa- search has revealed several pos- tical meridian. Two of the siblings thy in this family. sible molecular bases for chiasmal had a pure median chiasmal syn- It is impossible to determine if maldevelopment.5-12 Retinal gan- drome when first evaluated and their the visual defects were congenital or glion cell axons are believed to re- visual acuity and color sense dur- acquired. In all 3 patients, the neuro- spond to specific cues in their envi- ing many years of observation ophthalmic abnormalities were dis- ronment during development as they showed no abnormalities. Al- covered incidentally when each pa- migrate toward the optic chiasm. though the visual field defect in pa- tient was asymptomatic. Two of the Cell surface proteins on neurons or tient 3 is bitemporal, her slightly re- patients had normal findings on rou- glia in the chiasmal region may help

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©1999 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 to direct axonal processes to their ap- thy that is recessively inherited. Al- reditary optic atrophy with bitemporal field de- fects. Arch Ophthalmol. 1958;60:479-484. propriate destinations in the ipsilat- though there are several possible 4. Votruba M, Fitzke FW, Holder GE, Carter A, eral or contralateral optic tract and mechanisms for selective loss of Bhattacharya SS, Moore AT. Clinical features lateral geniculate nucleus. The loss crossing axonal fibers in the optic in affected individuals from 21 pedigrees with dominant optic atrophy. Arch Ophthalmol. 1998; of signals and/or growth factors that chiasm, it is unclear which may be 116:351-358. maintain the survival of fibers des- affected in this hereditary optic neu- 5. Harris R, Sabatelli LM, Seeger MA. Guidance tined to cross in the chiasm may lead ropathy. Current research in cues at the drosophila CNS midline: identifi- cation and characterization of two drosophila to their selective loss and subse- progress studying the molecular cues netrin/UNC-6 homologs. Neuron. 1996;17: quently to bitemporal visual field de- involved in the control of axonal 217-228. fects. There are even cell surface pro- crossing at midline structures may 6. Ishii N, Wadsworth WG, Stem BD, Culotti JG, Hedgecock EM. UNC-6, a laminin-related pro- teins such as the protein product of contribute to the identification and tein, guides cell and pioneer axon migrations the gene roundabout that are be- treatment of the hereditary genetic in C elegans. Neuron. 1992;9:873-881. 7. Serafini T, Kennedy TE, Galko MJ, Mirzayan lieved to repel axons from crossing defect responsible for this pheno- C, Jessell TM, Tessier-Lavigne M. The netrins 10 midline structures. It is possible type. define a family of axon outgrowth-promoting that the absence of this protein at a proteins homologous to C. elegans UNC-6. Cell. Howard D. Pomeranz, MD, PhD 1994;78:409-424. stage where retinal ganglion cell 8. Kennedy TE, Serafini T, dela Torre JR, Tessier- axons from the inferonasal regions Baltimore, Md Lavigne M. Netrins are diffusible chemotropic of the ipsilateral and contralateral Simmons Lessell, MD factors for commissural axons in the embry- onic spinal cord. Cell. 1994;78:425-435. eyes are approaching the midline Boston, Mass 9. Mitchell K J, Doyle JL, Serafini T, et al. Ge- structures of the optic chiasm may netic analysis of netrin genes in drosophila: preclude survival of the retinal gan- netrins guide CNS commissural axons and Corresponding author: Simmons Les- peripheral motor axons. Neuron. 1996;17: glion cells. Alternatively, loss of fac- sell, MD, Neuro-ophthalmology Unit 203-215. tors that maintain or influence neu- 10. Kidd T, Brose K, Mitchell KJ, et al. Round- Massachusetts Eye and Ear Infir- about controls axon crossing of the CNS mid- ronal metabolism or synaptic mary, Department of Ophthalmol- line and defines a novel subfamily of evolu- connections between retinal gan- ogy, Harvard Medical School, 243 tionarily conserved guidance receptors. Cell. glion cells and then postsynaptic tar- 1998;92:205-215. Charles St, Boston, MA 02114. 11. Kidd T, Russell C, Goodman CS, Tear G. Dos- gets in the lateral geniculate nucleus age-sensitive and complementary functions of may be responsible for selective loss 1. Raaf JE, Bair HL. Leber’s disease: report of four roundabout and commisureless controls axon cases in one family. Am J Ophthalmol. 1938;21: crossing of the CNS midline. Neuron. 1998;20: of inferonasally located retinal gan- 384-389. 25-33. glion cells. 2. Weiner NC, Newman NJ, Lessell S, Johns DR, 12. Tear G, Hah-is R, Sutaria S, Kilomanski K, We believe that the siblings de- Lott MT, Wallace DC. Atypical Leber's heredi- Goodman CS, Seeger MA. Commisureless con- tary optic neuropathy with molecular confir- trols growth cone guidance across the CNS mid- scribed in this article have a novel mation. Arch Neurol. 1993;50:470-473. line in Drosophila and encodes a novel mem- hereditary chiasmal optic neuropa- 3. Manchester PT Jr, Calhoun FP Jr. Dominant he- brane protein. Neuron. 1996:16:501-514.

From the Archives of the ARCHIVES

A look at the past...

HOCHRJAKOW ligated the ureters in a number of dogs and rabbits and killed some of them after the appearance of uraemic symptoms (second day), and some were allowed to die of uræmia (second to fourth day). In another se- Cries he removed the ligature and killed the animals intervals, letting them live from a week to two months. The microscopic preparations of the retina were stained by the Ehrlich-Dogiel methylene-blue method. There were found gen- eral œdema of the retina, with vacuole formation in and about the ganglion cells, in the nuclear and reticular layers, in the varicose thickening of the nerve fibres and Mu¨ llers fibres, as well as swelling of the vascular endothelium and enlargement of the perivascular spaces. All these changes appeared in from 2 to 7 days and disappeared, after restoring the permeability of the ureters, within two months. Similar changes were found in the eyes of persons dead of uræmia. The author believes uræmic blindness with negative ophthalmoscopic findings to be due to the changes he describes in the retina.

Reference: Progress in ophthalmology. Arch Ophthalmol. 1897;26:639.

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