Novel therapeutic strategies to restore vision in ocular hypotony (STRETCH): results from a prospective pilot series

Abstract

Background/Aims

To report visual and anatomical outcomes following intravitreal hydroxypropylmethylcellulose (HPMC) for the treatment of chronic structural hypotony.

Methods

This study is a prospective interventional case series. Eight patients with chronic structural hypotony for more than 3 months, defined by an intraocular pressure (IOP) of <6.5 mm Hg. All patients had evidence of visual potential, clear cornea and a clear visual axis.

Patients received multiple intravitreal HPMC injections (70 µL–1400 µL), administered every 2–4 weeks until either pre-morbid axial length was achieved, an IOP of 10–15 mm Hg was sustained for 4 weeks without signs of hypotony, or axial length of the contralateral eye was reached. They were followed up for 12 months after the first intravitreal injection.

Results

Best corrected visual acuity (BCVA) logarithm of the minimum angle of resolution (LogMAR) improved in 87.5% of eyes, with one eye remaining stable. The initial BCVA range was 0.3–1.7 LogMAR, and the final range was 0.1–1.6 LogMAR. IOP increased in 87.5% of eyes, from an initial range of 1–5 mm Hg to 3–23 mm Hg. Axial length increased in 75% of eyes, with a median increase of 1 mm (range 0.6–2.9 mm).

Two adverse events occurred: uveitis flare-ups leading to loss of HPMC clarity in two eyes, managed with topical and intravitreal steroids, and two cases of temporary vision loss post-injection, resolved after paracentesis.

Conclusion

This is the first case series to use a structured protocol for intravitreal HPMC in chronic hypotony management. The treatment improved vision and restored ocular anatomy, showing promise for managing structural hypotony in eyes with visual potential.

WHAT IS ALREADY KNOWN ON THIS TOPIC

• Chronic structural hypotony is a vision-threatening condition with limited effective treatment options and poor long-term outcomes.

• Intravitreal viscoelastic agents have been used anecdotally to manage hypotony, but no structured protocols or prospective data have been published.

• There is no established standard of care for restoring ocular anatomy and function in eyes with structural hypotony and visual potential.

WHAT THIS STUDY ADDS

• This study demonstrates that intravitreal hydroxypropylmethylcellulose (HPMC), delivered via a structured protocol, can improve visual acuity, intraocular pressure and axial length in selected patients with chronic structural hypotony.

• These findings suggest a reproducible therapeutic strategy with potential to prevent irreversible ocular damage in eyes with visual potential.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

• This study supports the use of intravitreal HPMC as a viable therapeutic option for selected patients with chronic structural hypotony, offering a structured, protocol-driven approach that can be implemented in specialist clinical settings.

• It provides a foundation for future clinical trials and may inform the development of standardised treatment pathways for vision preservation in hypotony.

Introduction

The chronic ocular hypotony management remains a significant challenge.¹ This potentially sight-threatening condition² is defined clinically or numerically and can be subdivided into:

1. Numerical hypotony

   There is a lack of consensus regarding the intraocular pressure (IOP) threshold that defines hypotony. The highest value reported is <6.5 mm Hg (>3 SD below the mean), which we have adopted to encompass a broader range of patients, including as many individuals as possible with evidence of structural hypotony,^1–5 minimising the risk of under-diagnosis.

2. Structural hypotony

   Refers to low IOP in combination with anatomical changes directly caused by the low pressure, including:

• Corneal oedema and striae.

• Shallow anterior chamber.

• Phacodonesis or pseudophacodonesis and iridodonesis.

• Cyclitic membranes and synechiae.

• Choroidal folds.

• Optic disc swelling.

• Retinal thickening.

• Hypotony maculopathy.

• Change in refractive error.

• Cataract.

• Axial length reduction.

• Ciliochoroidal detachment.

• Tortuous retinal blood vessels.

• Retinal pigment epithelial changes in the macula.

• Rhegmatogenous retinal detachment.

• Ocular ischaemia.^3–5

• Phthisis.³

The causes of hypotony are diverse, including increased aqueous outflow (eg, glaucoma surgery, cyclodialysis cleft) or reduced production of aqueous by the ciliary body (eg, inflammation, cyclitic membrane).^6–8 If left untreated, the globe eventually deforms, leading to structural changes and phthisis.^6–8

The treatment depends on its cause, involving medical and surgical management; visual outcomes are often poor.^{3 6 9}

Previous reports describe successful management of structural hypotony with intravitreal viscoelastic injections; however, without standardised protocols or structured data collection.^{1 7 8 10}

We describe a case series of patients with chronic structural hypotony treated with intravitreal injections of Eyefill HD (Bausch+Lomb),¹¹ a highly purified solution of 2% hydroxypropylmethylcellulose (HPMC) dispersive viscoelastic, primarily used in cataract surgery to improve visualisation and protect the corneal endothelium, repurposed here for the treatment of hypotony.

Moorfields Eye Hospital Hypotony Service outline

Established in 2021, the Hypotony Service manages complex cases through a multidisciplinary approach, incorporating expertise from uveitis, glaucoma, cornea, vitreoretinal, electrophysiology and ocular ultrasound specialists to maximise vision in eyes with chronic hypotony. Patients are clinically phenotyped and evaluated for reversible causes of low pressure.

Methods

Inclusion criteria

• Chronic hypotony (>3 months or >6 months after the last revision of over-draining filtration surgery).

• IOP <6.5 mm Hg.

• At least one structural change.

• Visual potential presence.^{12 13}

Exclusion criteria

• IOP ≥6.5 mm Hg.

• Hypotony for <3 months or <6 months after glaucoma filtration surgery.

• Boston keratoprosthesis or another reason why IOP could not be accurately assessed.

• Inability to undertake intravitreal injections under local anaesthetic.

• Inability to commit to regular visits.

• Visual axis opacity.

• Reversible cause of hypotony.

Reversible causes

Patients with reversible causes were managed prior to considering intravitreal HPMC and were not included in the study. Those with over-draining filtration surgery were managed by their glaucoma team, while those with chronic retinal detachments were managed by their vitreoretinal team. Intraocular inflammation was treated with high-dose topical, intravitreal, oral or orbital floor steroids to determine if their effect might be beneficial.

Only when the primary cause had been addressed and hypotony persisted for over 3 months, resulting in structural change, was HPMC treatment considered as an adjunctive therapeutic measure rather than a substitute for definitive repair.

Clinical phenotyping

At all visits, anamnesis and ophthalmological examination, including Logarithm of the Minimum Angle of Resolution (LogMAR) best corrected visual acuity (BCVA),¹⁴ IOP using an Icare IC200 supine tonometer and Goldman applanation tonometer, slit-lamp biomicroscopy and funduscopy were performed.

All patients underwent multimodal imaging: Spectralis optical coherence tomography (OCT) (Heidelberg Engineering) 30° macular cube, to assess the central macular thickness (CMT) and presence of subretinal or intraretinal fluid, choroidal folds and epiretinal membranes; retinal peripapillary nerve fibre OCT module, to evaluate changes in retinal nerve fibre thickness over time; ultrasound B scans (Siemens ACUSON Juniper), for anatomical examination and to rule out other pathologies; and ultrasound biomicroscopy (Quantal Medical ABSolu), to document the morphology of the ciliary processes.

They were informed of the novel nature of the intervention, the relevant approvals, the known risks of intravitreal injections and the unknown risks of treating ocular hypotony using intravitreal HPMC.

‘Count Fingers’ and ‘Hand Movements’ visions were described as 1.7 and 2.1 LogMAR, respectively, and the change from 2.1 to 1.7 LogMAR was marked as one-line improvement.¹⁵

Patient involvement

A patient advisory group was created in 2022 to ensure the service addressed concerns relevant to them. They met at regular intervals throughout the year, and patient time was reimbursed by the Thomas Pocklington Trust charity. The protocol was iterated and approved in conjunction with them.

Treatment visits

After consultation and examination, the injection was performed and a final pressure was measured using Goldman Tonometer. Sodium Hyaluronate 0.1% drops (Ursapharma) as required and Chloramphenicol 0.5% drops (Martindale Pharma) four times a day for 5 days were given post procedure. Axial length was measured 20 min after each injection.

Treatment was considered complete when either the pre-morbid axial length was reached, or the presenting IOP was above 10 mm Hg with resolution of structural hypotony features.

Treatment failure

Treatment failure was defined as a shortening in axial length by ≥1 mm or a reduction of ≥2 lines BCVA on three consecutive visits.

Infection, pain and patient decision to stop treatment were all reasons to pause or stop treatment.

Electrophysiology

Visual potential was determined using electrophysiological tests. Patients underwent flash visual evoked potentials (VEPs) and full-field electroretinography (ERG) according to the International Society for Clinical Electrophysiology of Vision Standards.^{12 13} Pattern testing was only utilised as an adjunct in the evaluation of visual potential, as pattern tests (pattern VEPs and pattern ERGs) were significantly influenced by media opacities and structural abnormalities, as could occur in eyes with structural hypotony. The combination of a flash VEP and full-field ERGs within the reference range was used as an indicator of good visual potential. If a flash VEP and ERGs were present but anomalous, then the eye was considered to have a reasonable potential but with a guarded prognosis, with more weight given to an abnormal flash VEP than abnormal ERGs. Finally, an undetectable flash VEP was an indicator of poor visual potential, and the patient was excluded.

Premorbid axial length

Globe volume loss was quantified based on the axial length measured optically using the IOLMaster 700 (Zeiss). The premorbid axial length was ascertained using one of the following metrics (in descending order of preference):

• Pre-existing biometry (most accurate).

• Axial length of the fellow eye (if present and structurally normal).

• History of refractive error prior to the onset of hypotony.

All treatments aimed to restore ocular anatomy and increase the axial length back to its premorbid size.

Intravitreal injections of HPMC

Patients underwent injections of HPMC according to protocol (online supplemental table 1). Injections were carried out in an injection room with more than 10 air changes per hour in accordance with local infection control regulations. Eyefill HD was transferred into a 1 mL syringe with a 29G needle to measure the volume injected accurately. HPMC was injected under topical anaesthetic using standard intravitreal injection technique, 3.5 mm behind the limbus, aiming for the mid vitreous. The volume injected varied per patient. While injecting, the IOP was evaluated using a cotton bud, and it was formally tested at the end of the procedure. If patients reported loss of vision, a paracentesis was performed.

Results

Demographics and diagnosis

Seven consecutive patients (eight eyes) were selected to have intravitreal HPMC injections between 22 December 2021 and 26 July 2023. Their age at the time of the first injection ranged from 21 to 80 years (median of 40 years). Their diagnoses included chronic anterior uveitis (not associated with inflammatory arthritis), sarcoid uveitis, juvenile idiopathic arthritis-associated uveitis and Stickler’s syndrome (with previous retinal detachment surgery, secondary glaucoma, which was treated with tube surgery and posterior tube removal due to exposure of the plate).

BCVA improvement

The median initial BCVA was 1.15 LogMAR (range: 0.3–1.7), and the median final BCVA was 0.4 LogMAR (range: 0.1–1.6).

Figure 1 shows the mean change in BCVA over the course of treatment.

Figure 1. Change in best corrected visual acuity (BCVA) in logarithm of the minimum angle of resolution (LogMAR) before starting treatment and after 12 months of treatment.

Eyes 1, 2, 4, 5, 6, 7 and 8 showed an increase in the number of LogMAR lines read, ranging from 1 to 9 lines. The median improvement was 4.5 lines. No change was observed across the two time points in eye 3; however, a significant improvement was noted at month 7, when it improved to 0.0.

IOP changes

The median initial IOP was 3.5 mm Hg (range: 1–5 mm Hg). The median IOP 12 months after treatment initiation was 9 mm Hg (range: 3–23 mm Hg). Figure 2a illustrates the mean IOP pretreatment and post-treatment. Figure 2b illustrates the changes per eye with the IOP before and after treatment.

Figure 2. (a) Change in the intraocular pressure (IOP) from the initial visit to the final visit at month 12. (b) Changes per eye with the IOP before and after treatment.

Eyes 1, 2, 3, 4, 5, 6 and 8 demonstrated increased IOP, ranging from 6 mm Hg to 23 mm Hg at the final time point. The IOP in eye 7 decreased by 1 mm Hg at month 12. The median increase in IOP over the 12-month period was 5.5 mm Hg.

CMT variation

The median initial CMT was 379 µm (range: 227–779 µm). Over the course of treatment, the CMT decreased, with a final median CMT of 315 µm (range: 277–393 µm).

Eyes 1, 2, 3, 4, 5 and 6 had a reduction in CMT, ranging from 56 µm to 457 µm. Eyes 7 and 8 had an increase in CMT by 35 µm and 166 µm, respectively. The median reduction in CMT was 126 µm.

Figure 3 shows the variation in the CMT per treated eye.

Figure 3. Central macular thickness (CMT) variation per treated eye.

Axial length variation

The median initial axial length was 22.4 mm (range: 18.6 mm–24.9 mm). At the last visit, the median final axial length was 23.1 mm (range: 21.5 mm–24.8 mm).

Eyes 2, 3, 4, 5, 6 and 8 increased in axial length, ranging from 0.6 mm to 2.9 mm of growth. Eyes 1 and 7 showed a reduction of 0.1 mm. The median increase in axial length was 1 mm.

Figure 4a shows the mean change in axial length. Figure 4b shows the changes in axial length.

Figure 4. (a) Mean axial length (AL) change before treatment and 12 months after treatment. (b) AL change per eye.

Number of injections and volume injected

The median number of injections per eye was 9 (range: 4–13), with a median volume of 214 µL (range: 94–650 µL). The median total volume injected at 12 months was 2145 µL (range: 350–4380 µL).

Table 1 shows the number of injections and the average volume per eye.

Table 1. Number of injections and average volume per eye.

Eye number	Injections (n)	Average volume of injections (µL)	Total volume injected (µL)
1	4	650	2600
2	10	487	4380
3	11	169	1690
4	4	94	375
5	8	187	1500
6	8	100	800
7	11	240	2650
8	13	242	3150
Median	9	214	2145

Adverse events

Two adverse events were observed in four eyes (1, 3, 4 and 7).

Eyes 1 and 7 developed a uveitic flare during treatment, resulting in a loss of clarity of the HPMC within the vitreous chamber. This was managed with topical and intravitreal corticosteroids. Their vision subsequently improved; however, after completion of the study period, patient 1 was offered a vitrectomy with an HPMC refill. Eyes 3 and 4 experienced transient vision loss immediately following the 11th and 4th injections, respectively, which resolved after paracentesis.

Conclusion

Overall, treatment with intravitreal HPMC injections led to encouraging outcomes 12 months after its start. The results are illustrated in online supplemental figure 1.

Discussion

This case series explores the use of intravitreal HPMC to manage the structural complications of chronic ocular hypotony in patients without cornea decompensation. They were pseudophakic or aphakic and had clear ocular media at enrolment.

Patients with this condition are at risk of permanent visual loss from a variety of sequelae.^{1 2}

The objective of this treatment is not to replace the management of the fundamental aetiology of hypotony, but to provide a means of restoring globe integrity once reversible or surgically correctable causes have been excluded or addressed. For example, in cases of traumatic cyclodialysis cleft, over-filtration following glaucoma surgery or ongoing inflammation, targeted management remains the priority. However, in chronic structural hypotony—where the ciliary body has lost functional reserve or anatomical collapse threatens vision—intravitreal HPMC offered a pragmatic method to preserve ocular structure and function until more definitive recovery or surgical intervention becomes possible.

History of viscoelastic use for hypotony

The use of viscoelastic substances to treat hypotony is not new and began to appear in the literature in the 1980s. While previous reports have been encouraging, there is no published framework in which patients with hypotony could be managed in a structured manner.

HPMC was selected for the initial cohort of patients because of its distinctive physicochemical and rheological characteristics compared with other ophthalmic viscoelastic devices. This was based on the following assumptions:

• As a dispersive, non-ionic cellulose-based polymer, HPMC possesses moderate viscosity and a refractive index (approximately 1.336) close to that of the native vitreous, allowing it to diffuse evenly within the posterior segment without forming discrete pockets. This contrasts with cohesive sodium-hyaluronate-based viscoelastics, which tend to aggregate and are less evenly distributed in the vitreous cavity.

• There are fewer refractive interfaces using a dispersive viscoelastic in unvitrectomised eyes.

• The viscoelastic resistance of HPMC provides transient structural support to the globe, counteracting scleral collapse and thereby maintaining IOP.

• Its hydrophilic and biocompatible nature reduces the risk of inflammatory reaction while allowing gradual resorption over time.

Our clinical experience has been positive; however, there are clear drawbacks to using a hydrophilic substance that can opacify in the context of intraocular inflammation or haemorrhage. HPMC also has low surface tension¹⁶ and would be unlikely to support the retina in the context of a break and/or detachment. It remains unknown whether cohesive viscoelastics would be superior to dispersive products for this indication, or whether hyaluronic acid products outperform HPMC. Of note, HPMC has a distinctive ultrasound signal and appears to be well dispersed throughout the vitreous cavity (figure 5).

Figure 5. Ultrasound of eye 2 after the eight intravitreal injections with hydroxypropylmethylcellulose. Hyperechoic foci, seen in both images (white arrow), ‘twinkle’ depending on the angle of the ultrasound probe.

We adhered to a treatment protocol for patients with chronic ocular hypotony with visual potential. While our pilot study did not include a control group, our findings compare favourably with previously published reports using similar viscoelastic agents. Our data are consistent with other studies. 87.5% of patients experienced improved vision 12 months after starting treatment, with a median increase in IOP of 6.9 mm Hg. O’Connell et al6⁶ also described similar outcomes after intravitreal viscoelastic injections. Their patients were not treated to target with a variety of timepoints reported; however, they described 100% of patients (five eyes) improving vision with an average increase in IOP of 7.4 mm Hg. Similarly, Küçükerdönmez et al⁷ observed that vision improved after intravitreal or intracameral viscoelastic injections in 43.8% of the eyes, reduced in 25%, and remained unchanged in 31.2%.

The visual improvement in 87.5% of the eyes and median IOP gain of 5.5 mm Hg in our series is consistent with, or superior to, these previous observations, despite differences in agent composition and treatment frequency. These comparisons further support the potential value of a structured, protocol-driven approach using HPMC for this challenging condition.

The improvements we describe may have long-term benefits, preventing progression to permanent visual loss and phthisis.

Most treated eyes (75%) had an increase in axial length at 12 months. While multiple studies demonstrate that there is a small fluctuation in axial length in normal eyes,^{17 18} eyes with poor aqueous production are at higher risk of significant shortening¹⁹ due to an imbalance in the outflow:production ratio.^{17 18}

The variability in BCVA, IOP, CMT and axial length highlights the heterogeneous nature of the patient group as well as responses to HPMC injections. This underscores the need for standardised protocols and further research to identify factors that influence individual responses.

Defining endpoints

We chose axial length to be our metric of ‘ocular stretch’. This is an oversimplification of scleral expansion and contraction. Ideally, we would calculate a target ocular volume in the anterior and posterior segments at the start of treatment. This is not available in clinical practice, but there are reports of methods used to calculate it with MRI.²⁰ They currently assume the eye to be spherical rather than slightly ellipsoidal, thus need refining. Other studies^{21 22} use CT and MRI data passed through a neural network to estimate ocular volume. There may be an application for whole-eye OCT data, but there are no current reports of its use.

Epidemiology of structural hypotony

Reporting chronic hypotony in the patient diagnoses and certificate of visual impairment forms will help assess the scale of the problem. Documentation of chronic hypotony complications is not commonplace and needs to be promoted across the profession. A British Ophthalmic Surveillance Unit study to determine the minimum incidence of chronic structural hypotony has started in mid 2025 and will allow the scale of the condition to be reported.

Strengths and limitations

To our knowledge, this is the first prospective study of the effect of a protocol-driven hypotony treatment plan.

The 1-year follow-up period provides valuable insight into treatment efficacy and safety, but does not capture long-term outcomes or delayed adverse effects. Extended follow-up is necessary to assess its benefits durability and to monitor for any late complications or recurrence.

The small sample size and lack of a control group are significant limitations. Without a control group, it is difficult to attribute the outcomes solely to the injections, and there are no data published to account for natural disease progression or spontaneous improvement. To address these issues, randomised controlled trials should aim to establish more robust evidence and to differentiate the treatment effects from hypotony natural variations, crucial efforts to validate HPMC injections as a viable treatment option for chronic ocular hypotony.

In future reports, we will describe treatment strategies and outcomes for patients with structural changes requiring a stepwise approach, where hypotony is managed prior to either vitreoretinal and/or corneal surgery (eg, patients with corneal decompensation secondary to low pressure).

In conclusion, the findings from this case series suggest that intravitreal HPMC injections may be a valuable addition to the management options for chronic structural ocular hypotony.

Data availability statement

Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.