Treatment options for chronic hypotony: a scoping review protocol

Abstract

Introduction

Chronic ocular hypotony (low intraocular pressure (IOP)) is a potentially sight-threatening condition. Although there is some controversy as to what constitutes non-physiological IOP, generally it is accepted as an IOP of 6.5 mm Hg or less, measured on three separate occasions and lasting for at least 3 months. There is a paucity of data in the literature describing the management of this potentially blinding condition. As such, there is no standardised treatment regime available and no consensus on expected visual prognosis.

Methods and analysis

The protocol for this scoping review will follow best practice as outlined by the JBI Scoping Review Methodology Group. This review will employ the population, concept, and context model for synthesis of the review questions. Databases searched will be Ovid Medline, Ovid Embase, The Cochrane Central Register of Controlled Trials, Web of Science and Scopus databases, as well as reference lists of relevant articles and the grey literature. Key concepts identified for conducting the literature search will be ‘Ocular hypotony’, ‘medication’ and ‘surgery’. Eligibility criteria include all adults undergoing medical or surgical treatment for chronic ocular hypotony. In order to validate this search strategy, we performed a sample search on Ovid Medline from 1946 to February 2024. Following the selection process, a custom form was developed in Microsoft Excel for data charting. We intend to summarise the data using a narrative model, with the study findings grouped based on similarities in the type of treatment and outcomes assessed.

Ethics and dissemination

Ethical approval was not required, as our review will only include published data. We will publish the review in an open-access, peer-reviewed journal and publicise our findings at international meetings.

STRENGTHS AND LIMITATIONS OF THIS STUDY.

• To the authors’ knowledge, this is the first treatment scoping review to be conducted on chronic ocular hypotony.

• We anticipate that the results of this review will substantially contribute to the existing body of knowledge, by signposting available treatment options and providing a reliable source of information for clinicians for this debilitating condition.

• The absence of randomised controlled trials targeting chronic hypotony does not diminish the significance of this review; rather, it sheds light on current clinical practice, underscores the lack of rigorous evidence-based data for this condition and informs areas of future research.

Introduction

Rationale

Chronic ocular hypotony poses a significant threat to vision. Although there is some controversy as to what constitutes non-physiological intraocular pressure (IOP), generally it is accepted as an IOP of 6.5 mm Hg or less, measured on three separate occasions and lasting for at least 3 months.1,3 There is a paucity of data in the literature describing the management of this potentially blinding condition. As such, there is no standardised treatment regime available and no consensus on expected visual prognosis. To the best of our knowledge, this is the first treatment scoping review to be conducted on chronic ocular hypotony.

Broadly speaking, chronic hypotony may be caused by decreased aqueous humour production or increased aqueous outflow, usually as a result of trauma, inflammation, glaucoma filtration surgery or certain medications.⁴ Trauma-induced hypotony may arise from open globe injury, cyclodialysis, ciliary body detachment or retinal detachment.³ Inflammatory conditions lead to reduced aqueous production by disrupting normal aqueous humour dynamics. Glaucoma surgery may be complicated by bleb leak or overfiltration, particularly if antimetabolites were used to prevent wound fibrosis.⁵ Systemic medications, such as carbonic anhydrase inhibitors, antihypertensives and hyperosmotic agents may also precipitate hypotony through a combination of mechanisms.^{3 4}

Clinically significant sequelae of low IOP include hypotony maculopathy, choroidal effusions, ciliochoroidal or retinal detachments, corneal oedema or astigmatism, optic disc oedema and phthisis bulbi. Ultimately, without appropriate diagnosis and targeted interventions, this may lead to blindness.^{3 4}

Conservative treatment measures involve the use of topical and systemic steroids in a bid to increase IOP, by inducing resistance in aqueous outflow. The role of cycloplegics in reducing aqueous outflow, and sympathomimetics in increased aqueous production has also been trialled.³

Surgical options have been more varied and arguably more successful. These include intravitreal injection of steroids, balanced salt solution, gas, silicone oil or viscoelastic substances. Of note, the use of viscoelastic in the eye represents an innovative approach in providing structural support and restoring normal IOP. Similarly, the recent use of perfluorocarbon gas has emerged as a promising solution for hypotony-associated maculopathy.⁶

Successful management of this condition relies on a comprehensive understanding of the underlying mechanisms, as well as awareness of available treatment options, to allow for targeted interventions and prevent potential sight-threatening complications.^{3 4}

The aim of this review is to identify the medical and surgical treatment options available for this condition. By analysing patient responses to reported interventions, we aim to summarise available treatment options and assess the extent by which they restore IOP and, consequently, visual acuity. This will improve clinician and patient education on the potential for early intervention to reverse or mitigate the debilitating effects of chronic hypotony.

The results of this review will extend to multiple relevant domains. For healthcare professionals, the collation and comparison of current treatments will allow better clinical decision-making which may be tailored to individual patient needs. This may also provide recommendations for future research. For patients, it holds the potential for a centralised, peer-reviewed source of information in this poorly researched condition. For policy-makers, it will inform on the burden of visual morbidity, and aid in appropriate resource allocation for relevant patient populations.

Objectives

As previously mentioned, there is no current ‘gold standard’ for the management of chronic ocular hypotony, as it is a rare and under-researched condition. This scoping review is the first to address the critical gap in our current clinical understanding of chronic hypotony:

1. What are the evidence-based medical and surgical treatment options available for chronic ocular hypotony?

2. How can I tailor these options to my patient’s needs in order to prevent further ocular complications?

3. How often do I need to repeat treatment to maintain its effect?

4. What is the expected visual prognosis for each of these options?

5. Is it possible to restore my patient’s vision?

Methods and analysis

The protocol for this scoping review will follow best practice as outlined by the JBI Scoping Review Methodology Group.⁷

The decision to undertake a scoping, rather than systematic, review was based on published guidance regarding methodological approaches when conducting evidence synthesis.⁸ In particular, scoping reviews are used when there is a lack of standardisation regarding the accepted definition of a condition. In this case, there are three broadly accepted definitions for chronic hypotony, each differing in IOP cut-off and minimum duration. This review will examine and report on these differences.

Additionally, this review aims to investigate the available designs and conduct of research on the treatment of chronic hypotony. Indeed, the lack of interest in this condition is highlighted by the paucity of high-quality evidence (eg, in the form of randomised controlled trials), with mainly case reports, descriptive, retrospective and interventional prospective studies available in the literature. These studies are unsuitable for any direct head-to-head comparisons and necessitate a scoping review. By identifying gaps in the literature and raising awareness of this blinding condition, this review will encourage the development of high-quality studies and eventually act as a precursor to a systematic review.

We will follow a methodological framework for conducting this review to ensure the research process undertaken is rigorous and transparent.⁹ We will include as a supplementary file the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist that documents data charting, synthesis and presentation.

Eligibility criteria

This scoping review will include studies of all designs and methodologies. There will be no limitations on publication dates or language. Only studies where the full text is available will be included.

The authors used the population, concept, and context model for synthesis of the review questions, to ensure that each component is well defined as recommended by best evidence-based practice⁸:

Population

Population include all adults (≥18 years old) with a diagnosis of chronic ocular hypotony (IOP ≤6.5 mm Hg for ≥3 months). The authors chose this definition as it encompasses the minimum criteria for the three most accepted definitions of chronic hypotony in the literature.

Concept

Medical treatment includes the use of any topical or systemic medication. Surgical treatment includes intravitreal injection of steroid implants, balanced salt solution, gas, silicone oil and/or viscoelastic substances. Primary outcome measures include evaluating the response to treatment in terms of IOP recovery, best corrected visual acuity, hypotony-associated complications or cosmetic appearance. Secondary outcome measures include determining the frequency and circumstances of treatment-resistant cases.

Context

We will include all eligible full-text articles from date of inception of specified databases.

Exclusion criteria

1. Where accurate tonometry-based IOP measurement was unfeasible, such as Boston Keratoprosthesis patients or those in whom only digital pressures were available.

2. Patients who have undergone glaucoma-related drainage device surgery, filtration surgery or laser treatment (including cyclodestructive procedures), as this review does not aim to describe interventions intended for managing postoperative glaucoma complications.

3. Patients with a history of retinal detachment.

4. Patients who have undergone surgical or laser correction of cyclodialysis cleft.

Search strategy

We will search Ovid Medline, Ovid Embase, The Cochrane Central Register of Controlled Trials, Web of Science and Scopus databases. Key concepts identified for conducting literature search are ‘Ocular hypotony’, ‘Medication’ and ‘Surgery’. When we carry out searches for the concepts, we will use Medical Subject Headingsand ‘free text terms’ with all synonyms and derivates of the terms. We will use Boolean operators ‘OR’ and ‘AND’ to combine search lines. All databases will be searched from inception date and no language limitations will be used. Furthermore, we will review reference lists of all included articles to identify any other potentially relevant studies. We will also search for grey literature on ocular hypotony treatment options. We will use a reference management software (Endnote; Clarivate, Philadelphia, Pennsylvania; available at https://endnote.com/) to manage search results and remove duplicate records. In order to validate this search strategy, we performed a sample search on Ovid Medline from 1946 to February 2024 (online supplemental file 1).

Study selection

Two reviewers (two of RK, KD, AS or DS) will independently screen the titles and abstracts of identified studies using the inclusion/exclusion criteria. The full-text article will then be retrieved for further screening, and two reviewers will independently assess each article to ensure suitability. Any discrepancies between the reviewers will be resolved by discussion, and a third reviewer (HP) will be consulted if necessary to reach a consensus. The studies will be assessed for suitability using a web-based screening software (Covidence; Veritas Health Innovation, Melbourne, Australia; available at http://www.covidence.org). A PRISMA flow diagram will be completed to summarise the study selection process.

Data charting

Following the selection process, a custom form will be developed in Microsoft Excel for data charting (table 1).⁷ A pilot data extraction will be performed by each of RK, KD, AS and DS. The authors expect data charting to be an iterative process, owing to the large variety of studies available.¹⁰ This may necessitate further addition of items to the data extraction form. Any amendments to the custom form will be agreed by group consensus. As per recommendations from the Cochrane Collaboration, any unclear information in eligible full-text articles will necessitate email contact to the study authors.

Table 1. Standardised data extraction form.

Domain	Description
Citation information	Title, authors, year of publication, country of origin
Study characteristics	Study type and design (eg, observational, qualitative, guideline, etc), sample size, population age, population gender
Study objectives	For example, visual recovery, enhance cosmetic appearance or to manage hypotony-associated complications
Eligibility criteria	Inclusion and exclusion criteria
Features of hypotony	Duration, lowest and highest recorded IOP, associated clinical findings
Aetiology of hypotony	For example, uveitis or trauma
Features of treatment	Type, frequency and duration, including concurrent or sequential use
Treatment outcomes	For example, best corrected visual acuity, IOP recovery, or any other study outcomes
Limitations	As described by authors, or any identified by the research team
Conclusions	Including gaps in the field as proposed by authors

Data synthesis

The data will be summarised using a narrative model. A direct head-to-head comparison between interventions will not be possible, due to variations in each study’s inclusion criteria and endpoints. Instead, the review will comprehensively assess the effectiveness of various interventions within the context of individual studies, and aggregate evidence to assess patterns of response and non-response among patients with chronic hypotony. This will allow us to identify patterns across the included studies and contextualise findings within the study design and setting.¹⁰ Our textual report will be supplemented with tables and descriptive statistics where possible.

Patient and public involvement

This review does not involve direct patient contact. However, this study holds the potential to generate substantial public interest, due to its implications on patient care and the broader healthcare system. As treatment for chronic hypotony to an extent depends on the aetiology of the condition, these results have the potential to predict who might benefit most from treatment, and risk stratify patients with this condition. This will allow clinicians to make informed decisions tailored to individual patients, understand the risk associated with each intervention and guide a better understanding of expected visual prognosis.

Ethics and dissemination

Ethical approval was not required, as our review will only include published data. We will publish the review in an open-access, peer-reviewed journal and publicise our findings at international meetings.