7/27/2019 1-s2.0-S0002939402014770-main

1/5

reports indicate that intraocular administration has noadverse effects on the retina,1 whereas others indicatepossible adverse effects on the retina.2 However, ICG mayaffect subsequent endophotocoagulation.

We report two cases in which ICG was used to facilitateILM peeling after which the Iris OcuLight 810-nm infrareddiode endolaser (Iris Medical Instruments, Inc, Mountain

View, California, USA) was applied. In both cases, laserapplied to intact ILM produced a more intense whitesuperficial-appearing burn in areas of intact ILM stained

with ICG than burns typical for this laser. In one of thetwo cases, burns were placed over intact ILM stained withICG and over the retina where the ILM had been peeled.The burns over intact ILM stained with ICG differedmarkedly from those where the ILM had been peeled. No

immediate adverse effects due to the difference in burnappearance were recognized.

CASE 1: A three-port pars plana vitrectomy was per-

formed on one eye of a 64-year-old man for a diabeticvitreous hemorrhage. After vitrectomy, diffuse edema wasobserved in the macula. The decision was made to peel theILM to facilitate recovery of the macular edema as previ-ously described.3 The ILM was peeled using ICG preparedas per protocol.1 Panretinal photocoagulation was then

attempted using the Iris OcuLight 810-nm infrared diodeendolaser. After a few laser burns it was noted that at lowpower and duration the burns over intact ILM wereexceptionally white and superficial in appearance. Noburns were placed in the area where the ILM was peeled.

CASE 2: A three-port pars plana vitrectomy with ILMpeeling was performed on one eye of a 54-year-old womanfor a stage 3 macular hole. The ILM was peeled in theposterior pole using ICG. A capillary bled briefly within

the peeled area. To treat the hemorrhage, a test burn wasfirst placed outside of the macula over intact ILM. Anintense superficial white burn appeared. Using the samelaser power and duration, a spot was applied to the area ofthe capillary; no retinal change was appreciated. An

adequate burn of typical appearance for this laser wasachieved using higher laser power and longer duration.

Indocyanine green is a tricarbocyanine dye with absor-bency between 790 nm and 815 nm (peak at 805 nm).4

Because of its optical properties and biocompatibility, ICG

has many medical applications. It has been used to measurecardiac output, hepatic function, and liver blood flow.4

Ophthalmologically, ICG is used for fundus angiography aswell as for visualization of basement membranes (anteriorcapsule of the lens and ILM of the retina) during surgery.

Experimentally, ICG has been used as a photosensitizingagent in tissue welding. Exposure to 805-nm light producessignificant amounts of heat and photocoagulation.5 Indo-cyanine green has also been used to treat vascular tumors.When stimulated by 808-nm light, the ICG produces a

cytotoxic photothermal reaction.6 We believe that we

have inadvertently witnessed a photothermal lighttissueinteraction at the level of the ILM. It seems likely thatILM stained with ICG absorbs the 810-nm laser energy,

producing an intense superficial spot instead of the typicaldeeper retinal burn.

We wish to alert users of infrared diode lasers of thispotential complication. If the use of both ICG and infrared

photocoagulation is contemplated in the same case, thephotocoagulation should be performed first if at all possi-ble. Use of ICG may prevent effective photocoagulation.

Theoretically, ICG in the choroid could also result insignificantly greater absorption, producing unanticipatedthermal effects.

Lasers of other wavelengths may not produce similar

reactions owing to the narrow absorption spectrum of ICG.The effects of other lasers as well as the effects ofendoillumination on ICG stained retina, especially in

cases of long duration, should be investigated.

REFERENCES

1. Da Mata AP, Burk SE, Riemann CD, et al. Indocyaninegreen-assisted peeling of the retinal internal limiting mem-brane during vitrectomy surgery for macular hole repair.Ophthalmology 2001;108:11871192.

2. Gandorfer A, Haritoglou C, Gass CA, et al. Indocyaninegreen-assisted peeling of the internal limiting membrane maycause retinal damage. Am J Ophthalmol 2001;132:431433.

3. Gandorfer A, Messmer EM, Ulbig MW, et al. Resolution ofdiabetic macular edema after surgical removal of the posteriorhyaloid and the internal limiting membrane. Retina 2000;20:126133.

4. Weisbecker C, Fraunfelder F, Rhee D, Tipperman R. Physi-

cians desk reference for ophthalmology. Montvale, NJ: Med-ical Economics, 1999:205207.

5. Decoste S, Farinelli W, Flotte T, Anderson R. Dye-enhancedlaser welding for skin closure. Laser Surg Med 1992;12:2532.

6. Chen WR, Adams RL, Heaton S, Dickey DT, Bartels KE,Nordquist RE. Chromophore-enhanced laser-tumor tissuephotothermal interaction using an 808-nm diode laser. Can-cer Lett 1995;88:1519.

Indocyanine Green AngiographicFindings in Systemic LupusErythematosus ChoroidopathyMagda Gharbiya, MD,

Francesco Bozzoni-Pantaleoni, MD,

Federico Augello, MD, and

Corrado Balacco-Gabrieli, MD

Accepted for publication March 3, 2002.From the Institute of Ophthalmology, University of Rome La Sapi-

enza, Rome, Italy.Inquiries to Magda Gharbiya, MD, Institute of Ophthalmology, Uni-

versity La Sapienza of Rome, Policlinico Umberto I, Viale del Poli-clinico, 155, 00161 Rome, Italy; fax: (39)06-4457706; e-mail:magda.gharbiya@tiscalinet.it

AMERICAN JOURNAL OF OPHTHALMOLOGY286 AUGUST 2002

7/27/2019 1-s2.0-S0002939402014770-main

2/5

PURPOSE: To report two patients affected with systemic

lupus erythematosus choroidopathy studied with combined

fluorescein angiography and indocyanine green angiogra-

phy. In particular, the presence of choroidal abnormalities

at indocyanine green angiography, which could not be

detected by fluorescein angiography, was studied.

DESIGN: Observational case reports.

METHODS: Retrospective review of the clinical and pho-tographic records of two patients with systemic lupus

erythematosus in whom choroidopathy developed.

RESULTS: Four findings were unveiled by indocyanine

green angiography: focal, transient hypofluorescent areas

in the very early phase; fuzziness of large choroidal

vessels with late diffuse zonal choroidal hyperfluores-

cence; poorly-defined areas of choroidal hypofluores-

cence visible up to the late phase; and focal cluster of

pinpoint spots of choroidal hyperfluorescence visible

from the intermediate to late phase.

CONCLUSION: Indocyanine green angiography can pro-

vide information that is not detectable by clinical orfluorescein angiographic examination in patients with

systemic lupus erythematosus choroidopathy. This infor-

mation may prove useful in better understanding the

pathogenesis of systemic lupus erythematosus choroid-

opathy. (Am J Ophthalmol 2002;134:286290.

2002 by Elsevier Science Inc. All rights reserved.)

SYSTEMIC LUPUS ERYTHEMATOSUS IS A CHRONIC, MUL-tisystemic immune disease characterized by the forma-tion of autoantibodies and circulating immune complexes

that cause tissue damage and organ dysfunction.

Systemic lupus erythematosus is known to involve

nearly all structures of the eye, including the external eye,

choroid, retina, and optic nerve. Choroidopathy with

serous neurosensory retinal detachment with or without

retinal pigment epithelial (pigment epithelium) detach-

ment is rare and is usually seen in severely ill or hyperten-

sive patients.1,2

We present two new cases of systemic lupus erythema-

tosusassociated choroidopathy, assessed by combined flu-

orescein and indocyanine green angiography. To our

knowledge, these are the first reports of indocyanine green

findings in this condition.

CASE 1: A 32-year-old woman with systemic lupus

erythematosus was referred in October 1999 for ophthal-

mic consultation.

In 1989, at age 22 years, a diagnosis of systemic lupus

erythematosus was made when she presented with acute

nephritis, thrombophlebitis of the left inferior limb, dis-

coid lupus, and a positive antinuclear antibody test. Since

then, she suffered only intermittent flares of her discoid

lupus. In October 1999, on the occasion of her last

cutaneous flare-up, she was referred for routine ophthalmic

examination. Her ocular history was noncontributory, and

she did not describe any visual problem. Antinuclearantibody test was positive with a titer of 1:320, anti

double-stranded DNA antibodies (anti-dsDNA) was posi-tive at 340 UI (normal: 100 to 250); immunoglobulin (Ig)G anticardiolipin was increased, whereas IgM anticardio-

lipin was at normal levels. Third (C3) and fourth (C4)complements of serum were within normal limits. Her

blood pressure was normal at 120/85 mm Hg. She wastaking 400 mg of hydroxychloroquine daily.

On ophthalmic examination, visual acuity was 20/20

with a refractive error of 1.00 diopter in both eyes.Pupillary responses and extraocular movements were nor-mal. Slit-lamp examination yielded normal results, andapplanation tensions were 14 mm Hg bilaterally. Ophthal-moscopy revealed in both eyes multiple spots of pigment

epithelial atrophy. The optic disk and retinal vessels werenormal; the overlying vitreous was clear. Fluorescein an-giography disclosed, bilaterally, either in the posterior poleor in the midperiphery, focal areas of hyperfluorescence,

which remained unchanged throughout the examination(Figure 1, top left).

Indocyanine green angiography unveiled bilaterally thefollowing findings: fuzziness of large choroidal vessels, fromthe early-to-intermediate phases, with late diffuse zonalchoroidal hyperfluorescence, either in the posterior pole or

in the midperiphery (Figure 1, top right and bottom left);large, poorly-defined areas of choroidal hypofluorescencefrom the intermediate-to-late phases, scattered in themidperiphery (Figure 1, bottom left); focal clusters ofpinpoint spots of indocyanine green choroidal hyperfluo-

rescence from the intermediate-to-late phases in the right

posterior pole and nasal quadrant, and in the left infero-temporal quadrant (Figure 1, top right and bottom right).

On standard electroretinogram, the amplitudes of thescotopic response and of the oscillatory potentials (Ops)

were reduced in both eyes. Automated visual field testingdemonstrated three paracentral superior relative defects inthe left eye and was normal in the right eye.

CASE 2: In May 2000, a 39-year-old woman with a

long-standing history of systemic lupus erythematosus,with arthritis, serositis, and lupus nephritis, was referred forroutine ophthalmic consultation. Her ocular history wasnegative. At the time of presentation, she had been inclinical remission for almost 1 year and she did not

complain of any visual disturbance. She was taking 400 mgof hydroxychloroquine daily. Her blood pressure was nor-mal at 110/70 mm Hg. Antinuclear antibody and anti-dsDNA tests were positive; IgG and IgM antiphospholipidantibodies were increased. Third (C3) and fourth (C4)

complements of serum were within normal limits.On ophthalmic examination, her visual acuity was

20/20 in both eyes, with no refractive error. Pupillaryresponses and extraocular movements were normal. Slit-lamp examination yielded normal results, and applanation

tensions were 12 mm Hg bilaterally. In the posterior pole

BRIEF REPORTSVOL. 134, NO. 2 287

7/27/2019 1-s2.0-S0002939402014770-main

3/5

bilaterally, areas of pigment epithelial mottling were

found. The optic disk and retinal vessels were normal; theoverlying vitreous was clear. Fluorescein angiography dis-closed, bilaterally, in the posterior pole multiple pinpointhypofluorescent and hyperfluorescent spots, which re-mained unchanged throughout the examination. One

hyperfluorescent spot of retinal pigment epithelium de-tachment was also present in the right perifoveal region(Figure 2, top left). On indocyanine green angiography,focal areas of transient choroidal hypofluorescence aroundthe optic disk and in the macular region were seen in the

very early phase (Figure 2, top right); fuzziness of largechoroidal vessels, from the early-to-intermediate phases,with late diffuse zonal choroidal hyperfluorescence wasseen either in the posterior pole or in the midperiphery(Figure 2, top right and bottom left); and poorly-defined

areas of choroidal hypofluorescence from the intermediate

to late phases, were also found in the midperiphery (Figure

2, bottom right).Although neither of our patients was evaluated in the

acute phase of her choroidal manifestations, indocyaninegreen angiography highlighted choroidal vascular abnor-malities, that were not evident either on fundus examina-

tion or on fluorescein angiography. Early, focal areas oftransient choroidal indocyanine green hypofluorescencesuggest choroidal filling delay. Fuzziness of large choroidalvessels with late diffuse zonal choroidal indocyanine greenhyperfluorescensce may indicate choroidal vascular leak-

age, probably caused by choroidal vessel wall damage,with abnormal diffusion and retention of the indocyaninegreen molecule in the choroidal stroma. Peripheral, poorly-defined areas of indocyanine green hypofluorescence onthe intermediate to the late phase of angiography may be

caused by an impairment of the physiologic indocyanine

FIGURE 1. (Case 1). Right eye. (Top left) Late-phase fluorescein angiogram. An area of hyperfluorescence (arrow) is barely visible

in the perifoveal region. (Top right) Intermediate-phase indocyanine green study. Note the presence of two round hyperfluorescentareas of indocyanine green abnormal diffusion. One focal cluster of pinpoint spots of indocyanine green hyper fluorescence (arrow)

is also seen, corresponding to the hyperfluorescent area detected by fluorescein angiography. (Bottom left) Intermediate-phase

indocyanine green study. Fuzzy choroidal vessels with indocyanine green zonal hyperfluorescence are surrounded by multiple poorly

defined areas of indocyanine green hypofluorescence (arrowheads) in the inferior midperiphery. (Bottom right) Intermediate-phase

indocyanine green study. Cluster of pinpoint spots of indocyanine green choroidal hyperfluorescence in the nasal quadrant.

AMERICAN JOURNAL OF OPHTHALMOLOGY288 AUGUST 2002

7/27/2019 1-s2.0-S0002939402014770-main

4/5

green diffusion from the fenestrated choriocapillaris be-

cause of vascular obstruction. Alternatively, they mayrepresent choroidal stromal atrophy with an intact, un-damaged retinal pigment epithelium, preventing the phys-iologic indocyanine green staining of the choroidal stroma.Focal cluster of pinpoint spots of indocyanine green

choroidal hyperfluorescence, appearing from the interme-diate to late phases, may indicate indocyanine greenstaining with localized abnormal fixing of the indocyaninegreen molecule. The first three features are all nonspecificand are seen in other inflammmatory or noninflammatory,

ocular and systemic diseases involving the choroid, includ-ing central serous chorioretinopathy. However, the occur-rence of late, focal cluster of pinpoint spots of indocyaninegreen hyperfluorescence in our first patient was found to bepeculiar. The pinpoint spots of hyperfluorescence may

represent immune deposits at the level of choroidal stroma,

the Bruch membrane, or retinal pigment epithelium base-

ment membrane, containing immunoglobulins and leuko-cytes, which have been shown to bind the indocyaninegreen molecule.3,4 Histopathological and immunofluores-cence studies of the eye in systemic lupus erythematosushave indeed shown inflammatory cell infiltrates within the

choroid in the form of diffuse lymphocytic infiltration, aswell as immunoglobulin and complement deposition in thebasement membrane of choroidal vessels and in the base-ment membrane of the retinal pigment epithelium.5,6

The pathogenesis of lupus choroidopathy remains still

unclear; immune complex deposition in the choriocapil-laris or autoantibody directed against the retinal pigmentepithelium, have been hypothesized.1,5,6 Systemic hyper-tension, resulting from lupus nephritis, and corticosteroidtherapy were also proposed to play a role in the develop-

ment of choroidal manifestations.1,2 Thus, choroidal vas-

FIGURE 2. (Case 2). Right eye. (Top left) Late-phase fluorescein angiogram shows hypohyperfluorescent spots and a small

hyperfluorescent pigment epithelial detachment in the perifoveal region (arrow). (Top right) Early phase indocyanine green studyshows a large indocyanine green hypofluorescent area of choroidal filling delay (arrowheads), surrounded by fuzzy choroidal vessels.

(Bottom left) Late-phase indocyanine green study shows diffuse choroidal indocyanine green hyperfluorescence in the posterior

pole. Note the indocyanine green hyperfluorescent spot (arrow) corresponds to the retinal pigment epithelium detachment seen on

fluorescein angiography. (Bottom right) Late-phase indocyanine green study highlights large, poorly-defined areas of indocyanine

green hypofluorescence (arrowheads) in the inferior nasal midperiphery.

BRIEF REPORTSVOL. 134, NO. 2 289

7/27/2019 1-s2.0-S0002939402014770-main

5/5

culopathy associated with systemic lupus erythematosusmay be secondary to vasculitis, systemic hypertension, andcorticosteroid therapy or probably to a variable combina-tion of these processes. Indocyanine green angiography

may be useful to expand our understanding of the patho-genesis of choroidal involvement in systemic lupus ery-thematosus, aiding the development of more rational and

effective therapeutic strategies.

REFERENCES

1. Jabs DA, Hanneken AM, Schachat AP, Fine SL. Choroid-opathy in systemic lupus erythematosus. Arch Ophthalmol1988;106:230234.

2. Nguyen QD, Uy HS, Akpek EK, Harper SL, Zacks DN, FosterCS. Choroidopathy of systemic lupus erythematosus. Lupus2000;9:288298.

3. Matsuda N, Ogura Y, Nishiwaki H, et al. Visualization ofleukocyte dynamics in the choroid with indocyanine green.Invest Ophthalmol Vis Sci 1996;37:22282233.

4. Chang AA, Lawrence SM, James TH, et al. Histologiclocalization of indocyanine green dye in aging primate andhuman ocular tissues with clinical angiographic correlation.Ophthalmology 1998;105:10601068.

5. Aronson A, Ordonez N, Diddie K, Ernest J. Immune-complexdeposition in the eye in systemic lupus erythematosus. ArchIntern Med 1979;139:13121313.

6. Schwartz M, Roberts J. Membranous and vascular choroidopa-thy: two patterns of immune deposits in systemic lupuserythematosus. Clin Immunol Immunopathol 1983;29:369380.

Histopathologic Study of Variation inSeverity of Retinitis Pigmentosa dueto the Dominant Rhodopsin MutationPro23HisKing To, MD, Michael Adamian, BS,

Thaddeus P. Dryja, MD, and

Eliot L. Berson, MD

PURPOSE: To compare histopathologic findings in anautopsy eye of an 87-year-old woman with retinitis

pigmentosa and the rhodopsin mutation Pro23His withfindings in an autopsy eye of a 77-year-old female relative(first cousin) with retinitis pigmentosa and the samemutation.

DESIGN: Histopathologic study.

METHODS: One eye from each patient was prepared for

light and electron microscopy within 5 hours after death.

Photoreceptor nuclear counts were performed.

RESULTS: Photoreceptor degeneration and intraretinal

bone spicule pigmentation were evident in both cases.

The younger patient had more extensive photoreceptor

loss and more intraretinal pigmentation than her olderrelative.

CONCLUSION: A marked variation in the extent of retinal

degeneration can be seen in two relatives with retinitis

pigmentosa and rhodopsin, Pro23His. This study sup-

ports the idea that factors other than the primary gene

defect are responsible for the severity of this condition.

(Am J Ophthalmol 2002;134:290293. 2002 by

Elsevier Science Inc. All rights reserved.)

RHODOPSIN GENE DEFECTS ACCOUNT FOR 25% OF CASES

with dominant retinitis pigmentosa in the United

States.1 The most common rhodopsin mutation in North

America is Pro23His, which is found in about one third of

patients with rhodopsin mutations. The present study was

done to evaluate histologically the variation in severity of

autosomal dominant RP in two first cousins with this

mutation.

Patient 226-903 died at age 87 and her affected first

cousin, patient 218-256, also female, died at age 77. Both

carried the rhodopsin mutation Pro23His heterozygously.

Eyes were obtained from both patients within 5 hours after

death. One eye from each patient was fixed in 2.5%

glutaraldehyde and 1% formaldehyde in phosphate buffer,

and processed for light and electron microscopy. Photore-

ceptor nuclei were counted on sectioned slides from six

different 100-m spans of retina in corresponding areas of

each eye in the parafovea.

Gross examination of the eye from the older patient (an

87-year-old woman) with milder disease showed sparse

intraretinal bone spicule pigment mainly in the inferior

temporal quadrant, a normal-appearing macula and supe-

rior fundus, and a tigroid-appearing inferior fundus (Figure

1, A). Gross examination of the eye from the younger

patient (a 77-year-old woman) with more severe disease

showed extensive intraretinal pigment around the periph-

ery (Figure 2, A). Microscopic examination showed that

the older cousin had up to three layers of cone nuclei in

the fovea and parafovea (Figure 1, B and D), whereas the

younger cousin had scattered areas of a single row of

photoreceptors in the fovea and parafovea (Figure 2, B and

D). The older cousin had numerous cone photoreceptors

with rudimentary outer segments in the superior midpe-

riphery (Figure 1, C and E), whereas the younger cousin

had no photoreceptors in the zone of intraretinal pigment

(Figure 2, C and E), a finding noted by others.2 The older

cousin had a photoreceptor nuclear count in the parafovea

Accepted for publication April 10, 2002.From the Berman-Gund Laboratory for the Study of Retinal Degener-

ations and the Ocular Molecular Genetics Institute, Harvard MedicalSchool, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts.

Supported by a center grant from the Foundation Fighting Blindness,Owings Mills, Maryland.

Inquiries to Eliot L. Berson, MD, Berman-Gund Laboratory, Massa-chusetts Eye and Ear Infirmary, 243 Charles St, Boston, MA 02114; fax:(617) 573-3216.

AMERICAN JOURNAL OF OPHTHALMOLOGY290 AUGUST 2002