In this study, we examined the clinical outcomes of a procedure that augments MP-TSCPC with limited CW-TSCPC in patients with refractory glaucoma. Results from this study suggest that the combined procedure is effective in lowering IOP and medication burden without compromising safety. Our data demonstrated a significant IOP reduction from baseline sustained through POY1.5 in a majority of cases, along with a significant reduction in medication burden over this period. Visual acuity was unchanged from baseline at all postoperative visits, suggestive of no long-term visual deficits from this procedure.
Despite the elevated risk of postoperative complications widely reported in CW-TSCPC compared to MP-TSCPC, complication rates in our study were lower than or comparable to previously reported complication rates following CW-TSCPC. In a review of 7 studies of CW-TSCPC, Souissi et al. reports chronic uveitis in 10.9% of patients [15]. In our study, AC inflammation following the combined procedure resolved in almost all cases during the early postoperative period, and transient AC inflammation in 3 other patients was either attributable to the additional glaucoma procedures they received or resolved spontaneously. Our rate of hypotony was lower than that reported in many studies of CW-TSPC, with rates ranging from 1.1 to as high as 39% in treated eyes [8, 16,17,18,19].
Singh et al., Chen et al., and Yildirim et al. report rates of hyphema in 1.1%, 12.0%, and 15.0% of patients following CW-TSCPC [20,21,22]. In our study, 7.9% of patients developed hyphema in the early postoperative follow-up period that spontaneously resolved in all but one patient with a concurrent diagnosis of malignant iris melanoma. It is difficult to conclude whether the onset of hyphema in this patient was related to the procedure itself or worsening ocular malignancy, though its incidence at POM3 is potentially suggestive of the latter. Additionally, CME rates of 2–12% for CW-TSCPC have been reported previously in the literature [7, 15, 23]. Given that 1 patient had CME prior to our operation, our incidence of CME in a single patient is on the lower end of these rates.
Considering that traditional CW-TSCPC is performed with a much higher number of burns than in our procedure (i.e., 20–28 burns vs. 5–12 burns), the lower risk of adverse outcomes in our study may be attributed to the lower total continuous laser energy delivered and burn area [8]. Furthermore, a review of MP-TSCPC studies reveals that augmenting MP-TSCPC with limited application of CW-TSCPC leads to a similar safety profile as performing MP-TSCPC alone. Emanuel et al., Nirappel et al., and Kuchar et al. report rates of hypotony following MP-TSCPC in 7.1%, 11.8%, and 26.3% of eyes [11, 24, 25]. Studies of MP-TSCPC have noted anterior chamber inflammation in up to 48.8% of eyes [24]. As mentioned earlier, we did note the incidence of CME in one patient which was not reported in the above studies of MP-TSCPC. However, this did not compromise vision. Thus, our results suggest that augmenting MP-TSCPC with limited CW-TSCPC is possibly safer than CW-TSCPC alone and may more closely approximate the safety profile of MP-TSCPC.
Additionally, our Kaplan–Meier analysis demonstrated a high cumulative success rate of 80.8% at POY1 given our success criteria of IOP reduction ≥ 30%, which was more strict than the 20% IOP reduction criteria used by many other papers [26]. When an even stricter criteria of 50% IOP reduction was applied to our data, the cumulative success rate was 71.6% at POY1, higher than the 59.6% success rate at POY1 achieved by Garcia et al. using only MP-TSCPC and a less restrictive IOP reduction criteria of 20% [26]. It has been well-documented that the IOP-lowering effect of MP-TSCPC appears to wane over time [1]. For example, while Zarrour et al. reported that 86.7% of patients undergoing MP-TSCPC achieved surgical success at 1 month post-treatment (defined as IOP reduction ≥ 20% from baseline), success rates decreased progressively to 67.1% at 6 months and 56.7% in 1 year [27]. A similar decline in success over time was noted in our results, decreasing from 80.8 at POY1 to 65% POY1.5 using a more stringent success criteria of IOP reduction ≥ 30%. Interestingly, it appears that patients treated with combined MP-CPC and CW-TSCPC did not experience a decline in success that was as drastic as those seen in other studies. These results again suggest a significant and more sustained benefit in IOP reduction from our combined procedure involving MP-TSCPC and CW-TSCPC compared to MP-TSCPC alone.
Considering that baseline IOP has been shown to correlate with the magnitude of IOP reduction, it is also important to note our significant IOP reduction of 15.1 mmHg at POY1 in relation to our average preoperative IOP of 27.9 mmHg [24]. In comparison, Vernon et al. demonstrated an average IOP reduction of 10.67 mmHg in their cohort with preoperative IOP ≤ 30 mmHg [6]. This correlation between baseline IOP and magnitude of IOP reduction was present in our Cox proportional hazard regression analysis, where every one-unit increase in preoperative IOP reduced the hazard of clinical failure by 14–15% (depending on whether the IOP reduction ≥ 30% or IOP reduction ≥ 50% success criteria was utilized). This suggests that a higher preoperative IOP is associated with a larger IOP reduction postoperatively and higher likelihood of clinical success.
Altogether, the safety and efficacy findings from the combined procedure suggest that blending the safety profile of MP-TSCPC with the IOP-lowering efficacy of CW-TSCPC may lead to effective IOP reduction without sight-threatening complications. It makes sense that complementing MP-TSCPC with a second, mechanistically different cyclophotogoaluative modality to target the ciliary body would lead to more definitive inhibition of aqueous humor production than MP-TSCPC alone. Furthermore, a limited application of CW-TSCPC in the combined procedure may likely lead to less dissipation of laser energy to surrounding tissues and therefore fewer side effects than those seen in full application of CW-TSCPC [1]. The methodology of this combined procedure, particularly the specific number of CW-TSCPC spots that should be applied based on preoperative IOP, can likely be further optimized through additional studies to minimize off-target effects and enhance the safety profile even further.
The limitations of this study include small sample size, a retrospective design, complex patient population, lack of a control group for direct comparison, and short follow-up time period for some patients. The wide range in follow-up lengths was likely attributable to the fact that some patients required a second glaucoma procedure soon after the first combined procedure, and these patients are censored from all analyses following the second procedure, thus limiting the follow-up length to that time point. Additionally, we were unable to find a similar control group for comparison for two reasons: (1) the population of patients who have undergone MP-TSCPC with these settings at our institution was limited; and (2) most of the patients in this study have a complex glaucoma history involving multiple mechanisms as well as failed medications and procedures. Together, these limitations may affect generalizability of the results. This risk for selection bias was mitigated in the study design by recruiting all patients who underwent combined treatment with MP-TSCPC and CW-TSCPC over a 17-month window instead of randomly sampling patients during this period.
The patient population in our study had refractory glaucoma, as evidenced by the large proportion of patients with severe (81.6%) and mixed-mechanism glaucoma (50.0%), elevated IOP (up to 47 mmHg), high preoperative medication burden (mean of 3.8 ± 1.2 medications), and a history of failed IOP-lowering procedures. Furthermore, given that our institution is a tertiary referral center, the patients in this study likely had more complex glaucoma than patients in a non-tertiary setting. Nevertheless, our combined procedure achieved significant reductions in IOP and medication burden while preserving long-term VA in our patients.
In summary, our results confirm that this combined treatment with MP-TSCPC and CW-TSCPC is a relatively safe and effective procedure that should be considered in patients with refractory glaucoma. Our findings are promising and point to a significant IOP-lowering effect and decrease in medication burden without greater risk of postoperative complications. Moreover, our combined procedure did not have any sight-threatening complications, given no significant decreases in VA at any follow-up time point. Further studies exploring a larger cohort of patients across multiple providers over a longer period of time would allow us to better characterize the longer-term effects of this combined procedure and determine the optimal number of CW-TSCPC spots for a given IOP. Likewise, a prospective study comparing CW-TSCPC, MP-TSCPC, and the combination of the two procedures would be very helpful to directly compare the outcomes of these procedures.