Pathogenic Implications of Subretinal Gas Migration Through Pits andAtypical Colobomas of the Optic Nerve

Objective  To describe subretinal migration of gas and silicone oil in a seriesof patients with congenital cavitary optic disc anomalies and to further clarifythe pathogenesis of the associated maculopathy.

Methods  Medical records of 4 female patients, aged 8 to 34 years, who developedsubretinal gas migration after vitreous surgery for macular detachment associatedwith cavitary optic disc anomalies were reviewed. A theoretical model wasused to calculate the pressure differential required to induce subretinalgas migration through an optic pit.

Results  The 4 patients had bilateral atypical optic nerve colobomas or a unilaterallarge optic pit. A definite defect in the tissue overlying the disc excavationcould be seen in one eye, and intraoperative drainage of subretinal fluidthrough the disc anomaly was possible in all cases. Subretinal migration ofgas or silicone oil was seen intraoperatively in one case and first appearedbetween 1 and 17 days postoperatively in the remaining cases. Theoreticalcalculations suggest that the pressure differential required for migrationof gas through a small defect in the roof of a cavitary disc lesion is withinthe range of expected fluctuations in cerebrospinal fluid pressure.

Conclusions  These observations provide clinical confirmation of a defect in tissueoverlying cavitary optic disc anomalies and imply interconnections betweenthe vitreous cavity, subarachnoid space, and subretinal space. We theorizethat intermittent pressure gradients resulting from normal variations in intracranialpressure play a critical role in the pathogenesis of retinopathy associatedwith cavitary disc anomalies.

Congenital cavitary anomalies of the optic nerve that may be associatedwith serous detachments of the macula include optic disc pit, optic nervecoloboma (typical and atypical), and morning glory disc anomaly.^1-4 Frankmacular detachment appears to be preceded by the accumulation of intraretinalfluid emanating from the disc anomaly and constituting an unusual form ofretinoschisis-like separation.⁵ Subsequentlythere is breakthrough of fluid into the subretinal space leading to detachmentof the macula and occasionally larger areas of the retina. The origin of thefluid and precise pathogenesis of macular detachment associated with cavitaryoptic disc anomalies remain unclear.

We present 4 cases of retinal detachment associated with excavated opticdisc anomalies in which vitreous surgery was complicated by subretinal migrationof gas and silicone oil. This rare and unexpected event cannot readily beexplained by the principles known to govern the behavior of intraocular gasand silicone oil. We believe that our clinical observations, coupled withrecent optical coherence tomographic findings and consideration of cerebrospinalfluid (CSF) dynamics, provide important new insights into the pathogenesisof the maculopathy complicating optic pits and related disc anomalies.

We retrospectively identified 4 patients who developed subretinal gasmigration after vitreous surgery for macular detachment associated with cavitaryoptic disc anomalies. The patients were derived from the practices of 4 retinaspecialists at 3 centers. One patient (case 1) was described in a previousreport.⁶ The medical records and availablefundus photographs were reviewed. Although institutional review board oversightwas not required for this chart review, each patient gave written informedconsent before undergoing surgical intervention. Using the physical principlesgoverning the behavior of intraocular gas, we calculated the theoretical pressuredifferential required for gas migration into an optic pit and compared thiswith information derived from a model of CSF pressure dynamics.

A 24-year-old woman was examined because of decreased and darkened visionin the central visual field of the right eye. The ocular history was significantfor mild myopia. The maternal family history was notable for glaucoma.

The visual acuity measured 6/200 OD and 20/20 OS. The anterior segmentwas normal in each eye. Examination of the right fundus demonstrated retinaldetachment involving the macula and superotemporal midperiphery and extendingto the temporal border of the optic nerve (Figure1). A stellate outer foveal defect was present, with a tiny full-thicknessdefect at the center of the fovea. The retina between the optic nerve andthe fovea had an appearance suggesting retinal thickening or schisis. Examinationof the optic disc demonstrated nasalization of the vessels with a deep, large,horizontally oval cup and a notch in the temporal neuroretinal rim. The leftdisc was anomalous, with a large cup and nasalization of disc vessels butno evidence of associated maculopathy (Figure1). B-scan ultrasonography of the right eye showed no evidence ofposterior vitreous detachment. Orbital ultrasound and computed tomographicscans were normal bilaterally.

The patient underwent pars plana vitrectomy with removal of the attachedposterior hyaloid, subretinal fluid drainage through a small retinotomy, fluid-gasexchange with 20% sulfur hexafluoride, and 10 days of postoperative face-downpositioning. Two months postoperatively, a moderate posterior subcapsularcataract was evident, along with a small macular hole and shallow subretinalfluid in the macula extending nasally to the optic disc. Contact lens examinationdemonstrated a defect in the tissue overlying the temporal aspect of the disccavitation.

When the subretinal fluid persisted 2 months later, krypton red laserburns were placed in 3 rows in the temporal juxtapapillary area. The patientthen underwent phacoemulsification with placement of an intraocular lens followedby repeat vitrectomy with fluid-gas exchange and postoperative prone positioning.Seven days postoperatively, several gas bubbles were noted in the subretinalspace between the optic disc and central macula (Figure 2). There was also gas trapped under neural tissue overlyingthe deep optic disc cavitation. The gas resolved during the subsequent 3 weeks.

Two months later, the patient noted an abrupt decline in vision in theright eye. Examination showed extensive detachment of the macular region andfluid communication with the small hole in the neural tissue over the opticdisc. A 50% fluid-gas exchange using 20% perfluoropropane was performed. After7 days of face-down positioning, the macula was flat and supplemental kryptonlaser was applied to the temporal aspect of the optic disc. After 10 additionaldays of face-down positioning, the patient noted an abrupt decline in visionand was found to have recurrent detachment of the posterior retina. Numeroussmall subretinal gas bubbles were located in the superior aspect of the detachment(Figure 3). An additional cluster ofbubbles appeared to be located within the schisis cavity in the papillomacularbundle area. No intraocular pressure measurement greater than 25 mm Hg wasrecorded at any postoperative examination.

Two months later, a total and highly bullous retinal detachment developed,obscuring a view of the optic disc and macula. No peripheral retinal breakswere found. The patient underwent repeat vitrectomy. During fluid-air exchange,subretinal fluid was drained through a small macular hole and over the opticdisc. Moderately heavy laser photocoagulation was applied around the entireoptic nerve, and lighter burns were placed in the papillomacular bundle andat the edge of the macular hole. Two weeks postoperatively, the visual acuityhad improved to 20/100 and the retina was completely flat (Figure 4). During the subsequent 10 years, the visual acuity remainedstable and the retina remained attached in the right eye.

An 8-year-old girl was diagnosed as having an optic pit in her lefteye on routine ophthalmologic examination. The visual acuity was 20/20 OU.Several months later, she returned for evaluation of central visual blurringin the left eye. The ocular and medical histories were notable only for mildmyopia. The visual acuity was 20/20 OD and 20/70 OS. The anterior segmentwas normal bilaterally. Fundus examination of the right eye showed a normaloptic disc and retina, with a cup-disc ratio of 0.5. Examination of the lefteye showed detachment of the macula associated with a deep excavation in alarge optic disc (Figure 5). No Weissring was present.

The patient underwent pars plana vitrectomy with removal of the posteriorhyaloid. During fluid-air exchange, subretinal fluid was drained through theoptic pit. Argon green laser was placed around the temporal juxtapapillaryarea. The vitreous cavity was filled with 10% perfluoropropane gas and thepatient was positioned face down. One week postoperatively, a subretinal gasbubble was noted in the macular region. This was allowed to resorb spontaneously.

One month later, a bullous retinal detachment was noted superiorly,with shallow detachment of the macula. Repeat vitrectomy with lensectomy,fluid-gas exchange, and scleral buckle was performed. No retinal breaks couldbe found. Recurrent retinal detachment inferiorly was noted 2 weeks postoperativelyand treated with repeat vitrectomy followed by injection of silicone oil.

Ten days postoperatively, the patient was found to have extensive siliconeoil in the subretinal space (Figure 6).She underwent repeat vitrectomy with silicone oil aspiration through the pitand placement of autologous blood over the optic pit. Endolaser treatmentwas performed for 360° around the optic nerve. Six months postoperatively,the visual acuity in the left eye was no light perception. The retina wascompletely attached, but extensive optic atrophy was present.

A 34-year-old woman had a 3-month history of central visual distortionand darkening in the left eye. The ocular and medical histories and familyocular history were unremarkable. Visual acuity was 20/20 OD and 20/50 OS.The anterior segments were normal.

The right fundus was normal apart from a large optic cup with a smallamount of fibroglial tissue and nasalization of disc vessels. There was alarge, deep, sharply delimited, and inferiorly decentered excavation in theleft disc, with a possible slitlike defect in the neural rim nasally (Figure 7). Biomicroscopy of the left macula showedevidence of retinoschisis and retinal striae in the papillomacular bundleand fovea, with a small serous outer-layer detachment in the central macula(Figure 8). No evidence of a posteriorvitreous detachment was present.

Laser photocoagulation was performed along the temporal aspect of theoptic nerve. Four months later, the visual acuity was 20/60 OS and a persistentmacular detachment was noted. The patient underwent pars plana vitrectomy.During fluid-air exchange, a portion of the subretinal fluid was aspiratedthrough the optic disc cavitation. At the conclusion of the procedure, subretinalgas was noted. The fluid-air exchange was repeated and the subretinal airwas removed.

At the 7-year follow-up examination, the visual acuity was 20/30 OS.The macula was attached with mild residual retinal striae, and laser scarswere present along the temporal margin of the optic nerve.

A 33-year-old woman had sudden loss of vision in her left eye. The familyhistory was notable for glaucoma. The visual acuity was 20/20 OD and 20/200OS. Results of anterior segment examination were normal. Fundus examinationshowed a large anomalous optic disc with a large cup (cup-disc ratio, 0.7)bilaterally. In addition, there was a small pit in the temporal aspect ofthe left disc accompanied by a large serous detachment of the macula.

The patient underwent pars plana vitrectomy. During fluid-air exchangeit was noted that the subretinal fluid could be aspirated via the optic pit.Endolaser photocoagulation was applied to the temporal juxtapapillary retina.On the first postoperative day, the macula was completely flat and additionallaser treatment was performed along the temporal margin of the disc.

Three weeks postoperatively, the visual acuity was 20/30 OS. Recurrentsubretinal fluid was noted adjacent to the optic pit. Pure perfluoropropanegas was injected into the vitreous cavity and the patient was placed in aprone position. One day later, multiple small gas bubbles were noted in thesubmacular space. The intraocular pressure was 14 mm Hg. The subretinal gasresolved during the subsequent month.

The patient returned 6 weeks later with an acute decline in vision tothe level of counting fingers. Examination demonstrated extensive retinaldetachment over the temporal half of the fundus, with no peripheral retinalbreaks. The patient underwent repeat vitrectomy with fluid-air exchange, laser,and subretinal fluid drainage through a retinotomy. Additional laser treatmentwas applied along the temporal margin of the optic disc. Two years postoperatively,the visual acuity was 20/50 OS and the retina was completely attached.

For a bubble of gas to pass through a retinal break, the force pushingthe bubble through the hole must exceed the surface tension of the gas bubbleon the edges of the hole.⁷ The force tendingto push the bubble through the hole is the product of the area of the hole(πR²) and the pressure difference across the hole (Δp).The force opposing prolapse is the surface-tension force, which is the productof 3 factors: the coefficient of surface tension (γ = 0.073N/m for a gas-water interface), the length of the margin of prolapse (circumferenceof the hole = 2πR), and the cosine of the contact angle (θ).When a gas bubble is about to pass through the hole, the radius of curvatureof the bubble equals the radius of the retinal hole. At this point the angleof contact is 0° and cos θ = 1. Therefore, the equationfor the pressure difference (in pascals) across the hole at the time of gasmigration simplifies to ΔPa = 2γ/R.⁷ Assuminga hole 200 μm in diameter, ΔPa = 2(0.073 N/m)/0.0001 m = 1460Pa = 148 mm H₂O. Thus, the pressure gradient requiredto push a gas bubble through a hole of this size is at least 148 mm H₂O (approximately 11 mm Hg).

Normal CSF pressure in the lateral recumbent position typically variesfrom 100 to 250 mm H₂O.⁸ In a caseseries of 58 patients ranging in age from 15 to 83 years, the mean CSF pressurewas 141 ± 19 mm H₂O.⁸ Intracranialpressure also appears to vary significantly over time. Studies of patientswith pseudotumor cerebri have demonstrated intracranial pressures varyingfrom 50 to 500 mm H₂O during 24-hour periods.⁸ Thereare few studies examining intracranial pressure over time in otherwise normalpatients.

Cerebrospinal fluid pressure is dependent in part on body position.The CSF can be modeled as a closed tube 700 mm in length with a pressure of140 mm H₂O in the horizontal position.⁹ Whenthe tube is reoriented vertically, the pressure within different parts ofthe tube is altered substantially (Figure 9).Although this model is not an exact replica of the human condition, it demonstratesthat changes in body position cause significant alterations in intracranialpressure. The magnitude of these changes easily exceeds the pressure gradientrequired for gas migration calculated in the previous subsection.

Typical coloboma of the optic disc is a congenital excavation, locatedinferonasally, that is believed to result from malclosure of the embryonicocular fissure.^2,4 Optic discpits are classically small and temporally located, but they appear to existalong a spectrum of congenital cavitary disc anomalies that are often referredto as atypical optic nerve colobomas.^1-3,10 Theembryologic basis for atypical optic nerve head colobomas, including opticpits, is unclear. Although our patients had negative family histories, theirdisc anomalies are similar to those previously described in several autosomaldominant pedigrees of atypical optic nerve colobomas and pits that were oftenassociated with nonrhegmatogenous detachments of the macula or more extensiveareas of retina.^1,3,10 Theoptic disc abnormalities in case 3 also bear some resemblance to those describedin the papillorenal syndrome, an autosomal dominant condition occasionallyassociated with serous retinal detachment.¹¹ Ourpatient had no personal or family history of renal disease.

Careful biomicroscopy and optical coherence tomographic imaging havedemonstrated that edema or a schisis-like separation in the outer retina appearsto be the initial pathogenic step in the development of serous macular detachmentcomplicating congenital cavitary optic disc anomalies.^5,12-14 Fluidfrom the disc excavation first accumulates within the retinal stroma, mostprominently in the outer plexiform layer. When severe, the edema mimics aretinoschisis cavity, but with intact vertical bridging retinal elements.The fluid later enters the subretinal space, either through an obvious outerlamellar foveal hole^5,12,13 orpossibly through minute invisible breaks in the outer retina. The schisis-likeseparation has been shown both to precede macular detachment and to invariablycommunicate with the optic disc, even when the associated macular detachmentdoes not.^12-14 Thepresence of schisis-like outer retinal edema most likely explains the highfrequency of treatment failure after photocoagulation to the juxtapapillaryretina in these eyes, although separation of the outer retina from the retinalpigment epithelium may also be a factor.

The most plausible sources of fluid responsible for the retinopathyassociated with optic pits and other cavitary disc anomalies are the vitreouscavity and the subarachnoid space. Evidence confirming a communication throughthe pit between the vitreous cavity and the subretinal space includes thefollowing: (1) india ink studies performed on collie dogs with cavitary discanomalies similar to human optic pits demonstrated leakage of ink from thevitreous cavity (but not from the subarachnoid space) into the subretinalspace via the optic pit.¹⁵ (2) During vitrectomy,intraoperative drainage of subretinal fluid through cavitary disc anomalieswas possible in our cases and in previously reported cases.^6,16,17 (3)In addition to the cases reported in this study, rare cases of subretinalmigration of vitreous substitutes through anomalous disc excavations havebeen reported previously. These include the migration of gas through an opticpit after outpatient perfluoropropane injection,¹⁸ themigration of both gas and silicone oil through a morning glory disc aftervitrectomy,¹⁶ and the intraoperative migrationof perfluorodecalin through a morning glory disc.¹⁹

Vitreous fluid is thought to gain access to anomalous disc cavitationsthrough small holes or breaks in overlying diaphanous membranes or neuroectodermaltissue. In our case 1, a gas bubble was observed trapped within the disc excavation,having passed through a small visible break in overlying neural tissue (Figure 2). Similar breaks have also been documentedin other series.^6,16-18,20 Thepossibility of vitreous traction associated with these breaks has been suggestedby clinical observations in several cases,^6,17,18,21 butits pathogenic role remains unclear. Obviously, vitreous traction played norole in the subretinal gas migration seen in our patients, since the migrationoccurred in each case after vitrectomy and peeling of the posterior corticalvitreous layer.

Several authors have suggested that CSF from the perineural subarachnoidspace may be responsible for the retinopathy complicating optic pits and relatedanomalies.^22-25 Histologically,optic nerve pits are herniations of dysplastic retina into a collagen-linedsac or pocket, which often extends posteriorly into the subarachnoid spacethrough a defect in the lamina cribrosa.^22,26 Theposterior aspect of the sac is typically a multiloculated fluid-filled space.Optical coherence tomographic studies have suggested a communication betweenthe schisis-like intraretinal space and a perineural space associated withthe optic pit.^12,13 Furthermore,communications between the subarachnoid space and subretinal space and betweenthe subarachnoid space and vitreous cavity have been proved clinically inpatients with the morning glory anomaly. In one case, metrizamide dye injectedinto the subarachnoid space migrated into the subretinal space but not intothe vitreous.²³ In a second case, gas injectedinto the vitreous at the time of optic nerve sheath fenestration for extensiveretinal detachment was noted to migrate into the perineural subarachnoid space.²⁴ Finally, the finding of relative hypotony in an eyewith an optic pit was attributed by the authors to drainage of intraocularfluid through the pit and into the subarachnoid space.²⁵

Our cases of gas and silicone oil migration from the vitreous into thesubretinal space clearly prove a communication between these 2 spaces throughthe cavitary disc anomalies. However, this phenomenon also suggests an unusualand complex pathogenesis, since surface tension considerations dictate thatmigration of a large intravitreal gas bubble through a small defect is impossiblewithout a large pressure gradient. Assuming a generous hole in the roof ofan optic pit of 200-μm diameter, we calculate that a pressure differentialacross the defect of at least 148 mm H₂O (11 mm Hg) is necessaryto force a gas bubble into the optic pit and then subretinal space. However,a significant pressure differential between the vitreous cavity and subretinalspace does not normally exist. We propose that the pressure differential requiredfor the subretinal migration of gas observed in our patients derives frompressure fluctuations in CSF that are transmitted to the optic pit via theperineural subarachnoid space.

Large fluctuations in intracranial and CSF pressure have been measuredin both normal and pathologic situations. Factors such as changes in bodyposition and venous pressure contribute to these fluctuations. Our calculations,based on the simplified models described in this report, suggest that thepressure differential required for migration of gas through a small defectin the roof of a cavitary disc lesion is well within the range of expectedfluctuations in CSF pressure. Such pressure alterations would be transmittedto the sac of the pit by CSF migration across the connective-tissue capsulein cases where the porous capsule is permeable to fluid (Figure 10). In pits with an impermeable capsule, we speculate thatpressure transmission could occur by small pressure-induced movements of thecapsule causing deformation of the pit sac (Figure 10). Thus, the pit conceivably functions like a bulb syringe,“sucking” fluid (or gas or silicone oil) into the pit sac duringa drop in intracranial pressure and then, with a rise in pressure, ejectingit from the sac. The fluid or gas exiting the pit would be expected to divide,part into the vitreous cavity and part into the retinoschisis cavity and eventuallythe subretinal space (Figure 3). Theexistence of such transient pressure gradients is suggested by the observationin one patient that vitreous debris overlying an optic pit was intermittentlysucked into the pit and later dislodged back into the posterior vitreous.²⁵

Our model demonstrates that normal fluctuations in intracranial pressurecan theoretically produce forces that are capable of exceeding the surfacetension of gas at a small break overlying an optic pit. The pressure gradientrequired for subretinal migration of materials with lower surface tension,such as silicone oil, perfluorocarbon liquid, and hyaluronic acid,²⁷ is lower, such that subretinal migration could occurmore easily and through smaller defects in the dysplastic tissue overlyingthe pit. Furthermore, since intravitreal gas can occasionally migrate throughcavitary disc anomalies into the subarachnoid space,²⁴ siliconeoil or perfluorocarbon liquid could potentially do so more easily and withunknown pathologic consequences. It may therefore be prudent to avoid theuse of liquid vitreous substitutes in the surgical management of cavitaryoptic disc anomalies.^16,19

A substantial pressure difference between the vitreous cavity and subretinalspace cannot develop in an eye with a mobile retina.⁷ However,fluctuations in intraocular pressure do affect the pressure differential betweenthe vitreous cavity and spaces outside the globe, such as the pit sac andperioptic subarachnoid space. Indeed, high intraocular pressure during fluid-airexchange likely contributed to the gas migration observed intraoperativelyin case 3. In the remaining cases, migration occurred postoperatively andwithout an apparent contribution by elevated intraocular pressure.

We believe that a pathogenic model that incorporates transient pressuregradients derived from the subarachnoid space is necessary to explain theunusual phenomenon of subretinal gas migration through cavitary disc anomalies.A unifying model must also include the observation that the anatomy of cavitarydisc anomalies varies from one eye to another. On the basis of the studiespreviously referred to, it seems clear that cavitary lesions communicate openlywith the vitreous cavity in some eyes, with the subarachnoid space in othereyes, and with both spaces in yet others. As Irvine et al²⁴ suggested,the vitreous, subarachnoid, and subretinal spaces may all be variably interconnectedbecause of the incomplete differentiation and porous nature of the herniatedtissues composing the optic nerve anomaly (Figure10). It follows that the subretinal fluid in a given case mightbe vitreous fluid, CSF, or an admixture of the two fluids. We speculate thatthe age at symptom onset in patients with congenital excavated disc lesionsmay depend in part on the anatomy of these interconnections. The typical ageat onset, in the third and fourth decades of life, may reflect the age atwhich sufficient liquid vitreous is available to be drawn into the pit.^6,18,20 On the other hand,CSF is more likely involved when the onset occurs in patients too young tohave liquefied vitreous, especially when the associated retinal detachmentis extensive.

The concept of a cavitary disc anomaly functioning as a mechanical pumpdriven by fluctuations in CSF pressure might also explain the peculiar retinoschisis-likeseparation and associated retinal detachment seen in these cases. Fluid movingpassively from the vitreous cavity through a pit would unlikely be driveninto the retinal stroma with sufficient force to cause a large schisis-likesplit and subsequent macular detachment. However, it is plausible that alterationsin CSF pressure, transmitted to the pit sac as described previously, wouldpump small aliquots of fluid under pressure into the retinal stroma. Thisfluid might be expected to gradually dissect a schisis cavity in the outerretina and eventually break into the subretinal space, often through a stellateouter foveal defect that has the appearance of having been created under force.

Subretinal migration of gas or silicone oil through cavitary disc anomaliesis an uncommon phenomenon. On the basis of our cases and those previouslyreported,^16,17,19,24 itappears that patients with large cavitary anomalies may be at greatest riskfor this complication. Although these eyes tend to develop large and recurrentretinal detachments, anatomic success is ultimately possible with the creationof a sufficient laser barrier in the juxtapapillary retina. Caution must beexercised in the application of this laser barrier, since the optic atrophyand poor visual outcome seen in case 2 may have resulted from overly intenselaser treatment extending 360° around the nerve head. A unifying modelof pathogenesis that we believe accounts for subretinal gas migration andother peculiar features of the retinopathy associated with cavitary disc anomaliesincludes 2 critical features: (1) variable interconnections between the vitreous,subarachnoid, and subretinal spaces and (2) transmission of intracranial pressurefluctuations to the pit via the perineural subarachnoid space.

Correspondence: Mark W. Johnson, MD, KelloggEye Center, 1000 Wall St, Ann Arbor, MI 48105 (markwj@umich.edu).

Submitted for Publication: September 17, 2003;final revision received February 27, 2004; accepted May 27, 2004.

Previous Presentation: This study was presentedin part at the annual meeting of the Association for Research in Vision andOphthalmology; May 4, 2000; Fort Lauderdale, Fla; and at the 18th Annual Meetingof the Vitreous Society; January 10, 2001; Cancun, Mexico.

Financial Disclosure: None.

Acknowledgment: We thank the following individualsfor providing case history material for this study: Susan G. Elner, MD, RobertR. Francis, MD, Brian T. Perkovich, MD, and Todd E. Schneiderman, MD.