Characterization of retinal hemorrhages delimited by the internal limiting membrane

Abstract

Clinically, hemorrhages at the vitreoretinal interface have been termed as ‘pre-retinal’ in location. However, there is a careful distinction to be made between sub-hyaloid and sub-internal limiting membrane (ILM) planes of blood collection. In the past half-century, a body of literature has accrued on sub-internal limiting membrane hemorrhage. We characterize the etiopathological, clinical, anatomical, and imaging characteristics of this entity (often misconstrued as sub-hyaloid hemorrhage). Management decisions are briefly described, and a unifying term of sub-internal limiting membrane macular hemorrhage is proposed to aid in further research.

The type of hemorrhage on fundus examination which appears to lie in the region anterior to the retina is usually labeled as a ‘pre-retinal hemorrhage’. This is imprecise, with reference to the actual space occupied by the hemorrhage – the sub-hyaloid or the sub-internal limiting membrane (ILM). Sub-ILM hemorrhage is a distinct entity with specific risk factors, clinical presentation, and management options.[1] Often, it is confused with sub-hyaloid hemorrhage, a term most practitioners are familiar with. We reviewed the existing literature and synthesized the various clinico-imaging features which may aid in the diagnosis, reporting, and research of this lesser-known entity.

Nomenclature

A histopathological study of “haemorrhagic retinoschisis” provided one of the earliest descriptions of hemorrhage between the nerve fiber layer and the internal limiting membrane.[2] Pre-retinal hemorrhages are traditionally thought to be sub-hyaloid in location, although sub-ILM hemorrhage may mimic the same.[3] This was in the pre-tomography era when the retinal and pre-retinal membranes could not be visualized in vivo. Today, one can precisely identify sub-ILM hemorrhages using optical coherence tomography (OCT). Several attributes differ between sub-hyaloid and sub-ILM hemorrhages, colloquially clubbed under ‘pre-retinal hemorrhage’ [Table 1].

Table 1.

Table differentiating sub-internal limiting hemorrhage from sub-hyaloid hemorrhage

Characteristics	Sub-ILM hemorrhage	Sub-hyaloid hemorrhage (SHH)
Shape and margin	Dome-shaped, well-demarcated - may be ‘boat-shaped’ but with a regular inferior margin	‘Boat-shaped’, irregular inferior margin
Surface reflex and ILM	Glistening reflex, reflected from the ILM overlying the hemorrhage	Dull reflex. Absence of sheen and striae (as observed from a taut-ILM reflection)
Mobility	Immobile	Tends to gravitate downward/change with head position
Surgical attributes	Confirmed by surgical peeling of the membrane - definitive method of identification. Location of hemosiderin in pigmented macrophages on the retinal side of ILM, confirms the sub-ILM location of bleed, along with histologic identification of the ILM	During surgical manipulation – SHH drains when the posterior hyaloid is breached and infusion fluid enters the sub-hyaloid space
Optical coherence tomography	Shows a hyper-reflective layer above the hemorrhage of high reflectivity. Sometimes a low reflective layer is seen anterior, suggestive of posterior hyaloid	Shows a hyperreflectivity posterior to a low-reflective layer (posterior hyaloid), usually extending anteriorly beyond the anterior extent of the scan
Rate of resolution	Resolves slower than SHH	Resolves faster than sub-ILM hemorrhage

A few other terms are used to describe this condition. Anatomically, sub-ILM hemorrhage is essentially intra-retinal, rather than pre-retinal, which makes the terminology of ‘macular hemorrhage’ or ‘sub-ILM hemorrhage’ a better descriptor.[4,5] Sometimes, this hemorrhage can be extra-macular, but more often, it involves the macula partly or completely; hence, the term “sub-ILM macular hemorrhage (SIH)” has also been accepted in the literature.[1,6] Clinically, distinguishing the bleed between the hyaloid and the ILM from that occurring between the ILM and the RNFL (retinal nerve fiber llayer) can be extremely difficult and perplexing at times. This review aims to expound upon sub-ILM hemorrhage or ‘hemorrhage delimited by ILM’ and discuss the pathophysiology, clinical features, and treatment modalities. For continuity and consistency, the abbreviation of SIH will be followed henceforth.

Methodology

This narrative review aimed to identify the clinical features and treatment options for SIH. A systematic literature search was conducted using the MEDLINE database accessed through the PubMed search engine. The search strategy included the following terms: “sub-ILM macular hemorrhage,” “sub-internal limiting membrane hemorrhage,” “sub-hyaloid hemorrhage,” “membranotomy,” and “hyaloidotomy.” The review focused on articles published in the English language up until December 2022. Abstracts of all relevant articles were initially screened by three authors (SKP, ASB, and SR), and the full texts of selected articles were carefully examined for further synthesis. Non-English articles, conference papers, and gray literature were excluded from the analysis. The review process followed the guidelines recommended by the ENTREQ checklist for qualitative studies, ensuring a systematic and rigorous approach to data synthesis.

Proposed Classifications

Etiologically, sub-ILM hemorrhage can be sub-divided into three types – vascular blow-out (secondary to intra-vascular pressure rise), mechanical (secondary to the forces acting on the globe due to trauma) and leakage (from abnormal vessels). Vascular pathologies leading to SIH can be localized or result from systemic vascular compromise, which dictates the outcome. While mechanical causes may result in isolated SIH, they usually have associated retinal insult. The prognosis of small and isolated SIH is usually good, whereas extensive lesions associated with SIH portend a worse prognosis. Hence, it is important to identify the underlying factor which resulted in the SIH. These causative factors modify the various clinical manifestations of SIH. We propose an etiological classification (based on location of the abnormality) that attempts to combine these features under the following headings – local retinovascular abnormalities, systemic central venous pressure abnormalities, and choroidal vascular abnormality with breakthrough.

Another factor affecting the prognosis is the quantum of damage to the underlying photoreceptors which may occur due to pressure effects from the tightly bound hemorrhage.[17] Photoreceptor integrity may be an indicator, which may not be apparent in the acute period, although swept-source optical coherence tomography (in a less dense hemorrhage) may indicate damage to the photoreceptors. From the intervention point of view, sub-ILM hemorrhage can further be classified into two types on optical coherence tomography – sub-ILM hemorrhage with or without underlying photoreceptor stress: with the former mandating early intervention. Further sub-ILM hemorrhage can occur in isolation or coexist with other types of hemorrhages like more commonly sub-hyaloid hemorrhage, sub-retinal hemorrhage, vitreous hemorrhage, or combination. Conditions where sub-ILM hemorrhage coexist with other often mandate early intervention. The clinical differentiation may help improve our understanding of the various imaging characteristics of SIH [Table 2].

Table 2.

Proposed classifications of sub-internal limiting hemorrhage

Classification based on etiopathology
(a) Vascular blow-out	(b) Mechanical	(c) Leaky vessels
Valsalva retinopathy (common)[7]	Contusion (closed globe injury)	Proliferative diabetic Retinopathy
Terson syndrome[4]	Penetrating ocular trauma[8]	Blood dyscrasias[3] immune thrombocytopenic purpura; bleeding diathesis, malaria,[9] dengue fever,[10] COVID-19[11,12]
Retinal arteriolar macro-aneurysm (RAM)[13]	Shaken-baby syndrome[14]	Macular neovascularization (rare)[15]
Retinal vein occlusion	Photic retinopathy[16]
Classification based on location of abnormality
(a) Local retinovascular abnormality	(b) Systemic central venous pressure (CVP) abnormality	(c) Choroidal vascular anomaly with breakthrough (limited by the ILM)
Retinal vein occlusion	Valsalva retinopathy	Macular neovascularization
Retinal vasculitis	Terson syndrome	Polypoidal choroidal vasculopathy
Proliferative diabetic retinopathy	Trauma/shaken baby syndrome
Retinal artery microaneurysm
Photic retinopathy- laser- induced injury
Post blunt trauma
Blood dyscrasias
Others: Malaria, dengue, COVID-19
Classification based on photoreceptor state: Sub-ILM hemorrhage with or without underlying photoreceptor stress
Sub-ILM hemorrhage in isolation or coexistent with other types of hemorrhages

Pathophysiology

The ILM is a basement membrane that establishes the contact and communication between the neuro-sensory retina and the posterior cortical vitreous, which is predominantly composed of type IV collagen fibers, glycosaminoglycans, laminin, and fibronectin. Histologically, there are three different zones of ILM: the basal, equatorial, and posterior zones. The ILM in the basal zone is thin, with a sub-ILM translucent zone containing delicate fibrils on the surface cytoplasm of underlying Müller cells that correlate with attachment plaques.[18] As it moves posteriorly, the ILM undergoes two key modifications: a progressive thickening of ILM and a lack of adhesion plaques.[18] This might explain why sub-ILM hemorrhages predominantly involve the posterior pole in adults. Because of the existence of the pre-macular bursa, an existing anatomic cavity is available for enlargement.[19] However, the ILM at the foveola is tightly adherent as hemi-desmosomes (from end-foot processes of the Muller cells) penetrate through the membrane and contact the intact posterior hyaloid.[20] This may lead to a hemorrhage that traverses around the central fovea [Fig. 1]. The role of ILM integrity has led to a hypothesis of a virtual ‘third’ blood and retinal barrier.[21]

Figure 1.

(a) Left eye color fundus photograph shows a well-defined sub-ILM hemorrhage of 3DD overlying the macula, with an incomplete double-ring sign (white arrow) seen temporally; (b) a large sub-ILM left eye hemorrhage in a diabetic retinopathy, spares the fovea due to the dense adhesion of ILM at foveal region. Exclamatory sign reflex (asterisk) is seen over the surface of the hemorrhage, indicative of a sub-ILM location; (c) right eye color fundus photograph in Valsalva retinopathy shows sub-ILM hemorrhage spreading supero-temporally over the macula, with an exclamatory sign reflex (asterisk) seen on its surface. A sub-hyaloid bleed is also indicated by an incomplete double-ring sign (white arrow) round the hemorrhage

The veins rostral to the heart lack valves, and any pressure change is immediately conveyed to the retinal vessels.[3] Valsalva maneuver causes an increase in intra-thoracic pressure, which is relayed to the peri-foveal capillaries, predisposing to bleeding, predominantly at the high-density capillary network that surrounds the foveal avascular zone.[3,22] The weak ILM in the macula also fosters blood to collect in the sub-ILM location. The definition of Terson syndrome has evolved; at present, it encompasses any intra-ocular hemorrhage following an acute rise in intra-cranial pressure which is usually after intra-cranial hemorrhage or traumatic brain injury.[23] However, the source of the blood has not yet been conclusively proven. According to one proposed theory, an increase in intra-cranial pressure promotes CSF effusion into the optic nerve sheath, resulting in dilatation of the retrobulbar aspect of the sheath in the orbit. The intra-venular capillary pressure rises as a result of the central retinal vein compression, leading to bleeding.[23] Owing to the thin walls and large lumen, post-capillary venules are especially sensitive to abrupt increases in intra-luminal pressure.[24]

The visual prognosis for patients with sub-ILM hemorrhage depends on the state of retinal anatomy before the incident, as is in Valsalva retinopathy or Terson syndrome. But the visual recovery is poor when treatment is delayed or hemorrhage is not resolved.

Mechanism of Damage

Iron and its metabolites are abundant in blood. Iron in a ferrous state catalyzes the conversion of hydrogen peroxide to reactive oxygen species (ROS) and hydroxy radicals.[25] The hydroxyl radicals can harm DNA, proteins, and lipids.[26,27] The retina is vulnerable to oxidative stress because of combined photo-oxidation and high oxygen tension caused by high perfusion.[25] Photoreceptor outer segments, which are phagocytosed by RPE cells daily, are rich in easily oxidized lipids and are susceptible to damage. A longer waiting time could incite the formation of the pre-retinal tractional membrane and proliferative vitreoretinopathy (PVR), causing irreversible damage.[5] It is also known that in response to cellular stimuli, such as a hemorrhage under the ILM, RPE can migrate through an intact retina, resulting in a PVR-like reaction.[28] Furthermore, mechanical harm by the compression of the underlying retinal tissue may cause secondary damage.[29] Prolonged contact of the retina with hemoglobin and its catabolites can perhaps trigger irrevocable toxic retinal damage. It is thought that blood delimited by the sub-ILM space creates a tension greater than the vitreous pressure upon the adjoining neuro-sensory retina.[30]

Clinical Features

Fundoscopic signs

The retinal signs on fundoscopy include a glistening light reflex over the dome of the sub-ILM hemorrhage which additionally may show surface striae, a ‘double ring’ sign (outer and inner rings represent sub-hyaloid and sub-ILM bleed, respectively) or ‘arcus retinalis’ (yellowish-white retinal arc)[4,31] [Fig. 1a]. In a flash-based fundus camera, the surface glistening light reflex would typically appear elongated and oval, almost resembling an exclamation (!) mark [see Fig. 1b and c]. While the taut ILM leads to the glistening reflex, the surface striae either may be an optical phenomenon due to the texture of the ILM or may represent minute ILM folds. The striae could also, hypothetically, be secondary to the altered blood interface underneath the ILM. A ‘double ring’ sign is seen when blood is present in a concentric ring around the sub-ILM hemorrhage, usually as flakes of hemorrhage that demarcate the posterior hyaloid.[4,7,32] Further, this sign may indicate a concurrent bleed in the two compartments, rather than a leak from the ILM into the sub-hyaloid region; however, this remains to be proven. Kumar et al.[31] described a novel clinical sign ‘arcus retinalis’ representing a yellowish incomplete or complete arc around the SIH. This sign was present in 50% (15 of 31 eyes) in their series of SIH of 2–6 weeks duration. The authors suggested that this phenomenon could be due to tractional forces on the underlying retina by the taut ILM edges. Arcus retinalis tends to disappear with time. A fluid level is usually noted in SILMMH along with a clear space superiorly (with serous fluid).[33] The classical boat-shaped sub-retinal hemorrhage is not always pathognomonic of a sub-hyaloid hemorrhage. In the setting of a substantially large sub-ILM space, blood cell components could gravitate and generate a boat-like image.

While these signs are usually seen in the early presentation, they may change their appearance with time. Spontaneous resolution of hemorrhage may occur with only a membranous cavity demarcating the area of the hemorrhage that might no longer be clinically detectable. A clinically visible empty cavity with a surface opening and detached ILM indicates prior laser membranotomy.[34] The detached ILM usually does not fall back in large detachments, following spontaneous resolution or laser membranotomy.

Optical coherence tomography

Spectral domain or swept source optical coherence tomography (OCT) provides distinguishing features of SIH during the early and late phases. Characteristically, two hyper-reflective lines at the vitreoretinal interface above the premacular hemorrhage, one with low optical reflectivity (corresponding to posterior hyaloid) and another with increased reflectivity and well-defined attachment to the retina (corresponding to the ILM), may be noted, which help in affirming the clinical diagnosis [Fig. 2].[35] The presence of vertical hyper-reflective structures at the level of the outer retina seen bordering the hemorrhage corresponds to the clinically visualized ‘arcus retinalis’.[31] The hyper-reflectivity at the outer retina may be secondary to localized traction on the retina by the ILM. A clear region of low reflectivity adjacent to an acute angle attachment of a dome-shaped hyper-reflective membrane indicates SIH. The upper border of the hemorrhage is the best area to discriminate between a sub-ILM and a sub-hyaloid hemorrhage on an OCT [Fig. 2b]. This is because the dense blood clot usually condenses in the lower part because of gravity. OCT scan passing superior to the hemorrhage identifies the presence of the two membranes – the ILM and posterior hyaloid.[36]

Figure 2.

Color fundus photograph and swept source OCT through a sub-ILM hemorrhage in eyes with proliferative diabetic retinopathy: (a and b) hyperreflectivity below (red arrow) and above (white arrow) the ILM suggesting coexistence of sub-ILM and sub hyaloid hemorrhage; (c and d) a dome-shaped hyper-reflective cavity with a convex hyper-reflective band on top, representing the detached ILM. A hyper-reflective band is also visible beneath the hemorrhage (white arrow) owing to the underlying RNFL compression

We report a novel finding of a horizontally oriented concave hyper-reflective line at the floor of the SIH [Fig. 2d]. In our opinion, it could be either an interface effect or due to the compressed nerve fiber/ganglion cell layer underneath the hemorrhage. A dome-shaped, well-demarcated, homogeneous hyper-reflectivity posterior to a curved hyper-reflective membrane (with/without central intense reflectivity of the ILM) and back-shadowing (clot/sediment) are the clinically relevant OCT markers of an SIH. Of special interest is the maintained foveolar-dip appearance noted when the ILM in this region detaches. It is worth mentioning that the initial homogeneous hyper-reflectivity may undergo changes during the resolution of the hemorrhage as the constituents and compactness of cellular components evolve over time.

Late findings may include a persistent premacular cavity visualized on OCT or an epiretinal membrane formation secondary to membranotomy.[19,37] A ragged-looking yellowish collection of altered blood may appear on the OCT as hyper-reflective material underneath the ILM, usually at the inferior aspect of the premacular cavity.[31] OCT scan can also help establish the amount and exact location of the residual hemorrhage post-membranotomy, which would otherwise be difficult to define clinically. Table 3 summarizes the clinical and OCT findings in SIH.

Table 3.

Clinical and OCT findings in Sub-ILM hemorrhage

Signs	Description and significance
Fundoscopic
Glistening light reflex	- Over the dome of the sub-ILM hemorrhage - Resembles an exclamation mark (!)
Double ring sign	- Outer and inner rings represent subhyaloid and sub-ILM bleed, respectively - Indicates a concurrent bleed in the two compartments
Arcus retinalis	- Yellowish-white retinal arc around the SIH - Represents tractional forces on the underlying retina by the taut ILM edges
Fluid level	Usually noted in SIH along with a clear space superiorly
Boat-shaped hemorrhage	-Not always pathognomonic of a subhyaloid hemorrhage - Blood cell components could gravitate and generate a boat-like image
Clinically visible empty cavity	- Indicates prior laser membranotomy - Hemorrhage may resolve spontaneously with a membranous cavity
OCT
Two distinct horizontal hyper-reflective lines at the vitreoretinal interface above the premacular hemorrhage [Refer: Fig. 3e and f]	- Line above with low optical reflectivity (fainter/patchy - posterior hyaloid) - Line below with increased reflectivity and attachment to the retina (ILM) - Better appreciated when performed just above the level of sedimented blood (best area to differentiate between a sub-ILM hemorrhage and a subhyaloid hemorrhage)
Vertical peg-like hyper-reflective structure at the level of the outer retina bordering the hemorrhage	- Corresponds to the clinically visualized ‘arcus retinalis’ - secondary to localized traction on the retina by the ILM - Fades away spontaneously over months
Clear region of low reflectivity [Refer: Fig. 3b]	- Adjacent to an acute angle attachment of a dome-shaped hyper-reflective membrane (ILM)
Horizontally oriented concave hyperreflective line at the floor of the sub-ILM hemorrhage [Fig. 2d arrow]	- Interface effect or compressed nerve fiber/ganglion cell layer underneath the hemorrhage
Dense hyperreflectivity with back shadowing of the premacular blood [Refer: Fig. 3e]	- Indicates blood clot or sedimented blood
Alterations during hemorrhage resolution	- Homogeneous hyper-reflectivity may alter due to changes in constituents and compactness of cellular components with time
Late findings [Refer: Fig. 3f]	- Persistent premacular cavity visualized on OCT - Epiretinal membrane formation - Ragged-looking yellowish collection of altered blood underneath the ILM at the inferior aspect of the premacular cavity

Angiographic modalities (dye-based and OCT angiography)

Fluorescein angiography usually demonstrates blocked fluorescence from the hemorrhage; it could help identify associated pathologies [as described in Table 2] of SIH. Of particular value is the detection of a retinal arteriolar macro-aneurysm (RAM). It is usually visualized when the SILMMH has resolved to a significant extent. Angiography is also helpful in detecting polypoidal choroidal vasculopathy associated with an SIH.[15]

There is not enough literature on non-invasive angiographic techniques such as OCT angiography. While a flow void will be expected due to the optical blocking properties of the hemorrhage, OCT-A may assist in elucidating the cause, for example, macular neovascularization.

Management

Observation for spontaneous resolution [Fig. 3a and b]

Figure 3.

(a and b) Spontaneous resolution of sub-ILM macular hemorrhage, images taken 1 month apart. (c-f) Resolution of sub-ILM hemorrhage following Nd-YAG membranotomy, images taken 2 months apart. A well-defined circular opening (arrow) is visible in figures d and f, which corresponds to the site of ILM opening

Leukemic patients may benefit from observation because most patients with acute leukemia are not good candidates for surgical intervention. There are reports of complete spontaneous resolution of the sub-ILM hemorrhage with good visual improvement, although the recovery period could be as long as 4–6 months [Fig. 3a and b].[38,39] Hemoglobin and its catabolites cause retinal injury. The development of the pre-retinal tractional membrane and proliferative vitreoretinopathy considerably delays resolutions. Also, a sub-ILM hemorrhage resolves more slowly than a sub-hyaloid hemorrhage.[22] Thus, early intervention can be considered in selected situations.[29]

Laser membranotomy (internal limiting membranotomy)

Puncturing the ILM by pulsed neodymium‐doped yttrium–aluminum–garnet (Nd: YAG) laser causes immediate drainage of the hemorrhage into the vitreous cavity when it is fresh, and blood is not clotted. It causes rapid resolution of the hemorrhage and vision restoration [Fig. 3c-f]. Following are some general tips for using the disruptive laser: (a) select a location that is away from the fovea, at the dependent section of the bleed, and ideally away from a major blood vessel;[40] (b) execute in hemorrhages larger than 3 disc diameter; this size has a cushioning effect and prevents injury to the underlying retina;[41] (c) it is preferable to increase energy gradually after starting low; (d) if the surface is not penetrated with 12 mJ, it is unlikely to be perforated with stronger energy.[40] However, energy levels up to 50 mJ have been attempted without apparent retinal injury.[42] The Goldman 3-mirror lens[40,43,44] has traditionally been employed to focus the Q-switched laser, whereas Area centralis[45] and Mainster wide field lenses were used for the frequency-doubled laser. To accomplish the membranotomy, a Q-switched laser in posterior mode has also been utilized in conjunction with an Abraham's capsulotomy lens.[46] In choosing laser membranotomy, the state of blood, rather than the duration, is more important.[47] Sahu et al.[44] have used a two-step technique of ILM/posterior hyaloid stretching using the argon laser, followed by a single penetrating burn to tear the membrane/hyaloid. Puthalath et al.[48] refined the method by applying a smaller, more powerful, penetrating burn placed between the two stretch burns. The posterior hyaloid may migrate because of the laser micro-explosion produced during the action of a Q-switched laser, making it much more challenging to penetrate. Additionally, the ocular media absorb most of its energy, possibly requiring multiple spots, and increased energy is needed to complete the task. Besides, one should know the complications of a Q-switched laser, such as retinal breaks, macular holes, and retinal detachments.[49] Choroidal rupture and CNVM formation have been reported with frequency-double Nd: YAG; these are more likely due to improper laser usage.[46]

Pneumatic displacement using intravitreal gas and tissue plasminogen activator

Tissue plasminogen activator (tPA) is a thrombolytic agent that produces plasmin, a fibrinolytic agent, that causes clot lysis. A gas bubble in the vitreous cavity displaces the lysed blood.[50] tPA is not required in recent bleeding since the soft clot can be dislodged with gas alone. It is more useful in people with a long history since the dissolution of the clot aids in displacement.[51] tPA, with a molecular weight of approximately 70kDa, is too big to breach the ILM.[52] However, it may diffuse into the sub-retinal space through the microlesions in the ILM caused by stretching from the hemorrhage.[53] In the setting of sub-retinal hemorrhage managed with tPA and gas injection, a gap of 3–6 hours before injecting an expansile gas should be enough to allow tPA migration across the retina.[54] A delay of 2–4 hours should be sufficient in the setting of SIH due to the close proximity of the blood to the vitreous body.[53]

Surgery: Vitrectomy with ILM peeling

Pars plana vitrectomy along with ILM peeling helps in immediate removal of the hemorrhage with early visual recovery. It also differentiates sub-ILM hemorrhage from sub-hyaloid hemorrhage [Fig. 4 a-c]. Vitrectomy is suggested for dense hemorrhage or in insufficient spontaneous absorption in Valsalva retinopathy. In specific cases, the foveal ILM is generally preserved by peeling the ILM outside the fovea and draining the hemorrhage using a backflush instrument to minimize the risk of developing macular hole after surgery. Hayamizu et al.[55] reported characteristic vertical hyper-reflectivity with ellipsoid zone/inter-digitation zone disruption on spectral domain OCT after vitrectomy for sub-ILM hemorrhage secondary to RAM. Immuno-histopathological analysis of the extracted ILM specimens [Fig. 5] has demonstrated cellular proliferation on the retinal surface of the ILM with staining for glial fibrillary acidic protein and cytokeratin 7.[29] Delayed surgery may lead to proliferative vitreoretinopathy-like changes beneath the ILM, while untreated cases can lead to persistent inner retinal changes.

Figure 4.

A case of sub-ILM hemorrhage, post ILM Peeling. Fundus image (a and b) shows the presence of arcus retinalis (arrow). OCT image (c) shows remnant of the detached ILM (arrow)

Figure 5.

Section through an ILM specimen that was excised following sub-ILM hemorrhage; a PAS-hematoxylin staining reveals a layer of partly pigmented cells and red blood cells on the undulated, retinal side of the ILM

While laser membranotomy and pneumatic displacement may be less resource-intensive options than a pars-plana vitrectomy, the attendant risks and failures of less invasive approaches may warrant an earlier switch to vitrectomy. Further comparative studies may help determine the best approach for SIH of varied intervals from onset of hemorrhage. Observation may be reserved for isolated SIH that is small (<1 DD size hemorrhage), foveal in location, and without evidence of underlying photoreceptor disruption/stress.

Conclusion

The under-diagnosis of SIH (as ‘sub-hyaloid’, probably due to the boat-shaped nature) can be avoided by utilizing the various clinical and investigative features described in this review. Qualification of the hemorrhage plane is of vital importance in management decisions, and knowledge of relevant funduscopic-tomographic features should assist the astute clinician in making the distinction. Apart from less invasive options (laser membranotomy and pneumatic displacement), vitrectomy has an increasingly important role to play in the management of SIH. Our summary of literature and proposed classification system will help reduce the usage of ‘pre-retinal hemorrhage’ in favor of well-defined clinico-imaging terms of SIH or SHH. Prospective studies on long-term outcomes of SIH and its classification can provide guidance in selecting appropriate therapy.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.