Review Reports - Balancing Pressure and Pills: Short-Term Outcomes of Goniotomy vs. Trabeculectomy in Adult Glaucoma

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This is an interesting study comparing efficacy and safety between trabeculectomy and goniotomy. The authors reported greater IOP reduction after trabeculectomy and greater reduction in glaucoma medications after goniotomy, reflecting the different target IOP between the two groups. In the era of MIGS evolution, such studies will be beneficial.

However, the study has substantial limitations, some of which have been reported by the authors. The study is retrospective; with a short follow-up period, the authors did not report whether cataract surgery had been performed along with the glaucoma surgery, nor did they report possible differences in the visual fields between the two groups. In some cases, two eyes from the same subject have also been included in the analyses. Very few OMNI cases (n=8) have been performed compared to Kahook (n=42) to draw meaningful conclusions between the two methods. This must be clarified also in the discussion and the limitations section of the study.

The introduction section is too long, with a lot of information not directly related to the subject.

Author Response

Comment: This is an interesting study comparing efficacy and safety between trabeculectomy and goniotomy. The authors reported greater IOP reduction after trabeculectomy and greater reduction in glaucoma medications after goniotomy, reflecting the different target IOP between the two groups. In the era of MIGS evolution, such studies will be beneficial.

The introduction section is too long, with a lot of information not directly related to the subject.

Reply:
We thank the reviewer for these insightful comments. We acknowledge the limitations noted, including the retrospective design, potential selection bias, and relatively short six-month follow-up period. These points have been explicitly addressed and expanded in the revised Discussion and Limitations sections. The inclusion of both eyes from some patients and the small number of OMNI cases (n = 8) are now discussed as factors that limit generalizability and statistical power. The Introduction has also been streamlined to focus more directly on the clinical problem, the rationale for comparing trabeculectomy and goniotomy, and the study hypothesis, reducing background material to improve clarity and flow. We believe these revisions strengthen the manuscript and directly address the reviewer’s concerns.

Reviewer 2 Report

Comments and Suggestions for Authors

Lines 111–119: The study aim is stated, but the main hypothesis is not clearly defined, nor is it explicit how this work differs from previous reports. Strengthening the rationale would help clarify the novelty.
Lines 134–144: The exclusion criteria are vague (“significant ocular comorbidities”). Please specify which conditions were considered and whether adjustments were made for glaucoma severity or baseline IOP when comparing groups.
Lines 151–152: Only t-tests and Fisher’s exact test are reported. Given baseline imbalances (e.g., IOP, sex), a multivariable approach such as ANCOVA or logistic regression would provide more robust comparisons.
Lines 187–194 and 260–264: The discussion should more directly address how higher baseline IOP in the trabeculectomy group may explain the greater reduction observed. Selection bias related to surgeon choice of procedure should also be elaborated.
Lines 265–270: The six-month follow-up is short for glaucoma outcomes. The limitations section should more strongly emphasize this and recommend longer prospective studies (≥2–3 years) to assess durability, late complications, and visual field outcomes.

Author Response

We thank the reviewer for the thoughtful and detailed feedback, which has been carefully addressed throughout the revised manuscript.

Comment (lines 111–119): The study aim and hypothesis are unclear.
Response: We added an explicit statement of the study aim and hypothesis at the end of the Introduction: “Therefore, our aim was to compare short-term (6-month) outcomes of intraocular pressure (IOP) change, change in number of glaucoma medications, and early complications between eyes undergoing goniotomy and those undergoing trabeculectomy at a single tertiary center. We hypothesized that trabeculectomy would yield a greater absolute IOP reduction, whereas both procedures would demonstrate a similar reduction in medication burden.”

Comment (lines 134–144): Exclusion criteria are vague.
Response: The Methods section has been revised to include specific ocular and systemic exclusion criteria. We now specify that eyes with uveitis, keratitis, pseudoexfoliation with zonular instability, advanced diabetic retinopathy, prior penetrating keratoplasty, or uncontrolled systemic infection were excluded.

Comment (lines 151–152): Statistical analysis is limited; justification for test selection not provided.
Response: The Methods section now clarifies that paired and independent t-tests were used for within- and between-group comparisons, and Fisher’s exact test for categorical data. We explain that no multivariate or adjusted analyses were performed, as the study was designed to reflect real-world, unadjusted outcomes.

Comment (lines 187–194, 260–264): Baseline IOP imbalance and selection bias may confound the findings.
Response: The Discussion now acknowledges that patients with higher baseline IOP or more advanced disease were preferentially selected for trabeculectomy, which likely contributed to the greater absolute IOP reduction observed. Surgeon preference and disease severity are now explicitly mentioned as sources of selection bias.

Comment (lines 265–270): The follow-up period is too short to evaluate long-term efficacy.
Response: The Limitations section now emphasizes that the six-month follow-up limits long-term interpretation of pressure stability and late complications, and recommends larger, prospective multicenter studies with 24–36-month follow-up to validate the findings and assess visual field outcomes.

Reviewer 3 Report

Comments and Suggestions for Authors

This is an interesting manuscript, aiming to evaluate short-term outcomes of goniotomy versus trabeculectomy. However, there are some issues needed to be addressed.

Major Concerns:

The significant difference in preoperative IOP between the two groups is a limitation. This potentially confounds the interpretation of the primary outcome. The greater IOP reduction in the trabeculectomy group is probably influenced by the higher initial IOP. A comparison of percent IOP reduction or performing ANOVA with adjustment for baseline IOP would be appropriate to evaluate the efficacy. While the authors acknowledge this limitation in the discussion, it weakens the conclusion that trabeculectomy is "more effective" in terms of IOP lowering.

The study currently does not use standardized success criteria. Reporting IOP reduction by a certain percentage, achievement of a target IOP with or without medications would provide more clinical context for the readers.

The authors report a statistically significant greater mean IOP reduction in trabeculectomy group. While statistically significant, the clinical importance of difference of approx. 3.4 mmHg over six months requires further elaboration.

The finding of a significantly greater medication reduction in the goniotomy group is intriguing, but the interpretation is currently limited by some uncertainty in methodology. The manuscript does not specify if there were standardized, pre-defined criteria for tapering or discontinuing postoperative medications. The observed difference may just reflect the preference of a surgeon in prescribing medication.

The finding that hyphema was significantly more frequent after trabeculectomy than goniotomy is intriguing and requires more elaboration. Is it in line with previous reported outcomes or is contrary to the established mechanistic profiles?

Minor Points:

The abstract states "Trabeculectomy resulted in a greater mean IOP reduction,". This is statistically true, but should be tempered with the context of the baseline imbalance.

In the Methods, the exclusion of "significant ocular comorbidities... such as infection" is vague. More specific criteria would be helpful.

Line 37 Please provide a reference to a global burden study

Line 42 “studies” implies to provide more than 1 reference

Line 54 Citing a longitudinal study showing progression in non-adherent patients would be benefitial for the manuscript

Lines 55-65 The entire section on barriers to adherence is descriptive but lacks specific citations. Please consider providing a citation here

Line 77 Please provide a reference on the changing glaucoma treatment paradigm

Line 94 The claim of "lower complication rates" for goniotomy compared to trabeculectomy is a key rationale for the study A comparative review would be appropriate here

Line 117 Please add a citation that discusses staged algorithm

Line 124 As this is a justification for the study, it should be a citation(s) here

Line 211 Cit 17 and 18 describe long-term outcome; probably, a reference to a paper discussing postoperative management of trabeculectomy is needed

Line 252 Please consider providing additional reference to a paper that assesses the higher number of visits/interventions.

Author Response

We thank the reviewer for the careful and constructive comments. We have addressed their points below and revised the manuscript accordingly.

Comment: “The significant difference in preoperative IOP between the two groups is a limitation. This potentially confounds the interpretation of the primary outcome.”
Response: We agree. In the Results and in the opening of the Discussion, we now state that the trabeculectomy group had a significantly higher baseline IOP and that the greater absolute IOP reduction “likely reflects” this higher starting pressure and surgeon selection of trabeculectomy for more advanced disease, rather than an inherent superiority of the procedure.

Comment: “A comparison of percent IOP reduction or performing ANOVA with adjustment for baseline IOP would be appropriate.”
Response: Because this was a retrospective, real-world series, we did not perform adjusted analyses. We clarified this in the Methods (“No statistical adjustments were made for baseline IOP or glaucoma severity, as the study design involved direct unadjusted group comparisons.”) and acknowledged it again in the Limitations as an important methodological limitation.

Comment: “Medication reduction may reflect surgeon preference; criteria for tapering not specified.”
Response: We clarified this in two places. In the Methods we now state that “Postoperative drop tapering and the decision to restart glaucoma medications were determined by the operating surgeon… No standardized postoperative medication protocol was used.” In the Discussion we added that this surgeon-dependent tapering “may have contributed to differences in medication reduction between groups,” so the finding should be interpreted cautiously.

Comment: “The finding that hyphema was significantly more frequent after trabeculectomy… requires more elaboration.”
Response: The Discussion now includes an explanatory sentence noting that direct comparative data between trabeculectomy and angle-based MIGS for hyphema are limited, but that hyphema after trabeculectomy has been reported and may be related to episcleral vessel manipulation or early hypotony. We also contrasted this with the usually transient, reflux-related microhyphema reported after MIGS and added supporting citations.

Comment: “Line 37 provide a reference to a global burden study / lines 42, 54–65, 77, 94, 117, 124 add citations.”
Response: We reviewed the Introduction and inserted the missing references in all places where we had mentioned limited studies . The global burden/evolving landscape statement now cites current glaucoma and MIGS reviews ; the adherence/barriers section now cites recent adherence papers ; the statement on lower complication rates of MIGS now cites safety/complication reviews; the staged algorithm sentence now cites a paper on MIGS within treatment sequencing; and the discussion of postoperative/visit burden now cites a trabeculectomy resource-utilization paper.

Comment: “Six-month follow-up is short; recommend stronger limitations and suggestion for longer studies.”
Response: The Limitations paragraph was rewritten to emphasize the 6-month horizon and now specifically recommends prospective multicenter studies with at least 24–36 months of follow-up to assess durability, late bleb-related events, and visual field outcomes.

Comment: “The conclusion that trabeculectomy is ‘more effective’ should be tempered.”
Response: We revised the Discussion and Conclusions to use neutral language: “trabeculectomy achieved a greater absolute reduction in IOP,” and we explicitly link this to higher baseline IOP and case selection, while highlighting that goniotomy provided a greater reduction in medication burden.

Overall, we have also toned down the main conclusion presented and rather presented it in context of our limitations with our better defined limitations paragraph. We have also toned down the conclusion mentioned in the abstract and presented it in context of higher baseline IOP.