International Journal of Ophthalmic PathologyISSN: 2324-8599

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Research Article, Int J Ophthalmic Pathol Vol: 4 Issue: 4

The Significance of Intraocular Pressure Alterations from Common Therapeutic Interventions: Preliminary Study with Clinical Implications

Ehtesham Shamsher, James S Schutz, Gabriele Thumann and Argyrios Chronopoulos*
Department of Ophthalmology, University Hospitals and School of Medicine, Geneva, Switzerland
Corresponding author : Argyrios Chronopoulos
Department of Ophthalmology, University Hospitals and School of Medicine, 1211 Geneva, Switzerland
Tel: 41 (0)22 372 8394
E-mail: [email protected]
Received: September 11, 2015 Accepted: October 21, 2015 Published: October 26, 2015
Citation: Shamsher E, Schutz JS, Thumann G, Chronopoulos A (2015) The Significance of Intraocular Pressure Alterations from Common Therapeutic Interventions: Preliminary Study with Clinical Implications. J Ophthalmic Pathol 4:4. doi:10.4172/2324-8599.1000169

Abstract

Objective: Human intraocular pressure (IOP) is normally controlled within narrow limits to maintain ocular form and firmness while allowing abundant retinal perfusion. Dangerous IOP elevation can occur when this equilibrium is challenged by common therapeutic manoeuvres which acutely increase intraocular volume or acutely decrease eye wall volume, such as intravitreal injection or scleral buckling. The purpose of this study is to confirm the relationship between acute intraocular volume changes and IOP elevation in an experimental model, review the pertinent literature, and discuss the ocular tolerance for acute IOP elevation as well as how to avoid related complications.

Methods: A porcine eye model was used to demonstrate the relationship between the volume of normal saline or air injected into the vitreous and resulting IOP increase. Incremental injections of normal saline or air were performed and IOP measured.

Results: Both normal saline and air injections of only 0.2 ml resulted in a dramatic increase of IOP. Injection of 0.3 ml or greater increased IOP to levels which potentially compromise retinal perfusion. Similar volumes of scleral buckling cause equivalent pressure elevations.

Conclusion: Dangerously elevated IOP caused by acute ocular volume changes associated with therapeutic intraocular injection or with scleral buckling may compromise retinal perfusion and may necessitate medical or surgical therapeutic manoeuvres. The safe interval for complete central retinal artery occlusion is probably only about 15 minutes rather than 90 minutes as commonly expressed in the literature.

Keywords: Intraocular pressure; Pressure volume relationship; Retinal ischemia; Intraocular injection; Scleral buckling

Keywords

Intraocular pressure; Pressure volume relationship; Retinal ischemia;Intraocular injection; scleral buckling

Introduction

Common therapeutic manoeuvres which either acutely increase intraocular volume or decrease the volume of the globe cause acute intraocular pressure (IOP) elevation which can endanger visual function by impairing perfusion to the retina and optic nerve head. Very high IOP may cause complete occlusion of the central retinal artery and choroidal circulation which nourish the retina. Inadvertent intraocular injection can elevate IOP sufficiently to cause ocular explosion [1-4]. Intraocular injections of antimicrobials, glucocorticosteroids, anti-VEGF agents, and intraocular gas are frequently performed, acutely raising IOP [5-11]. Scleral buckling, indentation of the eye wall, very commonly performed for retinal detachment repair, acutely decreases the volume of the vitreous cavity [12] similarly causing acutely elevated IOP. IOP elevation results because the human adult eye wall (cornea and sclera) are rather inelastic [13]. The purpose of this study is to demonstrate the relationship between acute alterations of intraocular volume and IOP elevation in a simple experimental model and to review the problem of IOP elevation caused by changes in intraocular volume using PubMed to search the English language literature using the terms: “intraocular pressure and volume”, “complications of intraocular injection”, “intraocular gas injection”, “scleral buckling and intraocular pressure”, “complications of scleral buckling”, and “complications of intraocular injection”. We discuss why the duration of complete occlusion of retinal perfusion which will cause permanent visual loss is much shorter than what is generally suggested as safe in the literature and how to avoid IOP related complications of intraocular injection and scleral buckling.

Materials and Methods

Sixteen fresh, age 6-7 months, white, porcine eyes obtained from a local slaughterhouse were used as an experimental model, chosen because of their similarity in morphology and size to human eyes [14]. The porcine eyes were brought to room temperature over 10 to 20 minutes in a water bath and external ocular tissues, fascia, nerves, vessels, muscles and lacrimal glands, were excised. Each experimental eye was wrapped loosely with cotton gauze to limit movement and supported on a small cup, cornea facing up. Because of hypotony from lack of perfusion and post-mortem aqueous outflow, each eye was intravitreally injected trans-sclerally at the equator with sufficient normal saline (NS), several tenths of a millilitre, to bring the IOP to 5-10 mmHg using a 30 gauge needle on a 1 ml syringe. All IOP measurements were performed with a Schiotz tonometer.
The 16 eyes were divided in two groups. Group 1 consisted of 7 eyes, injected with NS in 0.1 ml increments through the equatorial sclera using a 30 gauge needle on a 1 ml syringe; IOP was measured by Schiotz tonometry immediately after each incremental injection and recorded while the needle on the syringe was still in the eye in order to try to prevent leakage from the needle tract. No leakage was observed. The syringe was supported manually in order to avoid pressure on the eye wall.
Group 2 consisted of 9 eyes which received an intravitreal injection of either 0.1, 0.2 or 0.3 ml of air. The IOP was similarly measured by Schiotz tonometry immediately while the needle on the syringe was still in the eye. Incremental injections of air were not performed in order to eliminate any error introduced in the volume of injection by the compressibility of air caused by IOP elevation.

Results

The resulting IOP after incremental injections of NS is shown in Table 1. The mean IOP resulting from the injected volumes is displayed in Figure 1. Intravitreal injection of only 0.1 ml was sufficient to bring IOP from hypotony to upper normal levels in all experimental eyes while injection of 0.3 ml of NS resulted in critical elevation of IOP to a mean of 118 mmHg. Injection of 0.4 ml resulted in levels of IOP off scale (greater than 127.5 mmHg).
Figure 1: Mean IOP after incremental injections of NS in 7 porcine eyes.
Table 1: IOP elevation in 7 porcine eyes subjected to incremental intravitreal injections of NS. (OS = off scale, greater than 127.5 mm Hg).
The IOP elevation in Group 2 resulting from a single known volume of intravitreal air injection is displayed in Table 2 and Figure 2. The mean IOP change from each injected volume of air is demonstrated in Figure 3. Even though air is compressed by elevated IOP to occupy a smaller volume, the IOP change from any given volume of injected air does not appear to be different than for the same volume of NS in our experiment; if a difference is actually present, it is below the level of accuracy of our experimental measurements.
Table 2: IOP in 9 porcine eyes after a single injection of à specific volume of air.
Figure 2: IOP after a single air injection.
Figure 3: Mean IOP after a single air injection.

Discussion

The primary purpose of this study is to show the effect of acute changes in intraocular volume on IOP, specifically to explore the volume of intravitreal liquid or gas that can be injected without causing critical IOP elevation. A volume of as little as 0.2 ml of NS injection is likely to cause acute IOP elevation to abnormal levels. A volume of 0.3 ml NS injection in our study produced a mean IOP elevation of 115 mm Hg, similar to what has been previously described [15].
Given the physical properties of air which render it compressible, a volume of injected air or gas might be expected to cause a significantly smaller acute IOP elevation than injection of the same volume of NS. However, the IOP elevation from air injection was essentially the same as compared to en equal volume of NS in our experiment even when IOP was highly elevated to 115 mm Hg. This can be explained by the Boyle-Mariotte law which predicts that at constant temperature, the volume reduction of injected air with IOP elevation to 115 mmHg is only about 13%, shown in Table 3, which is clinically insignificant.
Table 3: Volume change of intravitreal air subjected to 115 mm HG IOP elevation.
Therapeutic intraocular injections of 0.1-0.2 ml of fluid and injections of 0.5 ml of gas for pneumatic retinopexy are routinely performed [9,10,16-19]. Small changes in intraocular volume of more than a few tenths of a millilitre are clinically significant, causing potentially dangerous IOP elevation which can compromise central retinal artery (CRA) and choroidal perfusion [20,21]. The CRA supplies inner layers of retina including the ganglion cells. The choroidal circulation supplies the outer retina including the photoreceptors and the optic nerve head [22]. Retinal vascular occlusion from high IOP, if complete and of sufficient duration, will result in retinal infarction with permanent visual loss. An important question in this context is how long can complete central retinal artery occlusion be tolerated without irreversible retinal damage? In vivo experiments on rats have demonstrated that an IOP elevation of 60-70 mmHg for at least 105 minutes can cause irreversible damage to the retina [23]. Clinically, the safe interval of complete CRA occlusion in the human before irreversible damage commences is generally accepted to be 90 minutes [24-28]. However, we feel that this may be incorrect and actually be much shorter. The 90 minute limit for “safe” CRA occlusion was obtained from experiments in anesthetized monkeys by clamping the CRA at its entry into the optic nerve, many millimetres behind the eyeball [25-26]. These experiments were conducted under barbiturate anaesthesia which has neuroprotective properties [29,30]. Furthermore clumping of the CRA at its entry into the optic nerve sheath does not produce a complete CRA occlusion because there is highly variable and often generous collateral circulation around and in the optic nerve at its scleral entry from the circle of Zinn-Haller, well distal to the clamped CRA, which provides anastomoses between the CRA and posterior ciliary arteries [31]. Moreover, there is controversy regarding the site of human CRA occlusions which have been suggested to be at the CRA dural entry through the optic nerve but without any evidence cited [32]. We agree with others that CRA occlusion is most likely to occur in or adjacent to the lamina cribrosa of the optic nerve, not many millimetres behind the eye [33-37] Consequently, most human CRA occlusions occur distal to the circle of Zinn-Haller and are probably not much compensated by circle of Zinn-Haller vascular anastomoses [38]. Furthermore, the retinal ganglion cell layer is central nervous system tissue comprising the optic nerve, cranial nerve I, and after 10-15 minutes of brain ischemia, neuronal infarction begins; consequently, after complete interruption of CRA perfusion for 15 minutes, retinal ganglion cell death occurs progressively [39,40].
In normal human eyes, acute IOP elevation rapidly decreases over 5-10 minutes because of increased aqueous outflow with elevated IOP. However, in eyes with an abnormal coefficient of outflow, eyes with glaucoma or a tendency to glaucoma, the pressure drops over a longer period of time and poses a greater threat to retinal and optic nerve head perfusion. Clinically, after acute iatrogenic high IOP elevation when the eyeball feels hard, the CRA may be visualized directly to monitor perfusion. If the CRA remains non-perfused for longer than 5-10 minutes, therapeutic manoeuvres to lower IOP may be performed to protect or restore retinal artery circulation, such as anterior chamber paracentesis of 0.1-0.2 ml of aqueous humor, similar aspiration of intravitreal air or fluid, intravenous acetazolamide or mannitol as well as administration of topical ocular hypotensive agents [41,42].
Acute ocular volume reduction by indentation of the sclera in scleral buckling is sufficient to cause clinically significant IOP elevation similarly. However, much larger volumes of buckling may be achieved without dangerous IOP elevation by lengthening the duration of buckling surgery so that ocular wall indentation is progressively increased over time which allows aqueous outflow to reduce elevated IOP, by using sponge buckles which are compressed by elevated IOP and progressively achieve their final volume over time as IOP gradually diminishes, by drainage of subretinal fluid or aqueous paracentesis which decrease intraocular volume, or by ocular hypotensive agents such as intravenous mannitol or acetazolamide. The use of such diuretic agents may cause a full bladder on the operating table and even acute urinary retention in susceptible males.
Our experimental study has a number of limitations. Variation in our results was caused by differences in intraocular volume between different porcine eyes, and differences in axial length, and compliance of the experimental eyes. Schiotz tonometry was chosen to measure IOP because it is simple to perform but has some limitations with respect to accuracy [43,44]. An important oversight in our experimental model was not performing control measurements of IOP for statistical analysis on control pig eyes nor on the experimental eyes in this small pilot study. Nevertheless, our findings are consistent with a study conducted on living patients receiving 0.1 ml intravitreal liquid injections [11]. We feel that our simple experimental model provides a veridical approximation of the ocular pressure-volume relationship comparison between intraocular injection of saline or gas which is clinically important in ophthalmic therapy.

Conclusion

Intraocular injection or scleral buckling volume which is clinically significant, sufficient to cause abnormal IOP elevation, is about 0.2 ml and in glaucomatous eyes, even an injection of 0.1 ml may cause unsafe pressure elevation. Intraocular injection of 0.3 ml can cause elevation of IOP sufficient to compromise CRA and choroidal circulation in some patients. The safe volume of injection of compressible gas is similar to fluid; a significantly larger volume of gas cannot be injected safely. The safe period of complete retinal vascular occlusion produced by acute IOP elevation is controversial; however, it is probably much less than 90 minutes which is generally accepted, closer to 15 minutes because the inner retina is central nervous system tissue.

Declaration of Interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

References

  1. BrarGS, Ram J, Dogra MR, Pandav SS, Sharma A, et al. (2002) Ocular explosionafter peribulbar anesthesia. J Cataract Refract Surg 28: 556-561.

  2. BullockJD, Warwar RE, Green WR (1998) Ocular explosion during cataract surgery: aclinical, histopathological, experimental, and biophysical study. Trans AmOphthalmol Soc 96: 243-276.

  3. BullockJD, Warwar RE, Green WR (1999) Ocular explosions from periocularanesthetic injections: a clinical, histopathologic, experimental, andbiophysical study. Ophthalmology 106:2341-2352

  4. MagnanteDO1, Bullock JD, Green WR (1997) Ocular explosion after peribulbaranesthesia: case report and experimental study. Ophthalmology 104:608-615.

  5. BaumJ, Peyman GA, Barza M (1982) Intravitreal administration of antibiotic inthe treatment of bacterial endophthalmitis. III. Consensus. SurvOphthalmol 26: 204-206.

  6. CunninghamET Jr, Wender JD (2010) Practical approach to the use of corticosteroidsin patients with uveitis. Can J Ophthalmol 45: 352-358.

  7. TripathyK, Sharma YR, R K, Chawla R, Gogia V, et al. (2015) Recent advances inmanagement of diabetic macular edema. Curr Diabetes Rev 11: 79-97.

  8. LuX, Sun X2 (2015) Profile of conbercept in the treatment of neovascularage-related macular degeneration. Drug Des Devel Ther 9: 2311-2320.

  9. FabianID, Kinori M, Efrati M, Alhalel A, Desatnik H, et al. (2013) Pneumaticretinopexy for the repair of primary rhegmatogenous retinal detachment: a10-year retrospective analysis. JAMA Ophthalmol 131: 166-171.

  10. ChanCK, Lin SG, Nuthi AS, Salib DM (2008) Pneumatic retinopexy for the repairof retinal detachments: a comprehensive review (1986-2007). SurvOphthalmol 53: 443-478.

  11. KotliarK, Maier M, Bauer S, Feucht N, Lohmann C, et al. (2007) Effect ofintravitreal injections and volume changes on intraocular pressure:clinical results and biomechanical model. Acta Ophthalmol Scand 85:777-781.

  12. MichelsRG (1986) Scleral buckling methods for rhegmatogenous retinal detachment.Retina 6: 1-49.

  13. Asejczyk-WidlickaM1, Pierscionek BK (2008) The elasticity and rigidity of the outer coatsof the eye. Br J Ophthalmol 92: 1415-1418.

  14. SanchezI, Martin R, Ussa F, Fernandez-Bueno I (2011) The parameters of theporcine eyeball. Graefes Arch Clin Exp Ophthalmol 249: 475-482.

  15. SilverDM, Geyer O (2000) Pressure-volume relation for the living human eye. CurrEye Res 20: 115-120.

  16. KuhnF, Aylward B (2014) Rhegmatogenous retinal detachment: a reappraisal ofits pathophysiology and treatment. Ophthalmic Res 51: 15-31.

  17. HwangJF, Chen SN, Lin CJ (2011) Treatment of inferior rhegmatogenous retinaldetachment by pneumatic retinopexy technique. Retina 31: 257-261.

  18. MandelcornED, Mandelcorn MS, Manusow JS (2015) Update on pneumatic retinopexy. CurrOpin Ophthalmol 26: 194-199.

  19. AbeT, Nakajima A, Nakamura H, Ishikawa M, Sakuragi S (1998) Intraocularpressure during pneumatic retinopexy. Ophthalmic Surg Lasers 29: 391-396.

  20. PolkJD, Rugaber C, Kohn G, Arenstein R, Fallon WF Jr (2002) Central retinalartery occlusion by proxy: a cause for sudden blindness in an airlinepassenger. Aviat Space Environ Med 73: 385-387.

  21. PERRYRB ROSE JC (1958) The clinical measurement of retinal arterial pressure.Circulation 18: 864-870.

  22. VarmaDD, Cugati S, Lee AW, Chen CS (2013) A review of central retinal arteryocclusion: clinical presentation and management. Eye (Lond) 27: 688-697.

  23. BuiBV, Batcha AH, Fletcher E, Wong VH, Fortune B (2013) Relationship betweenthe magnitude of intraocular pressure during an episode of acute elevationand retinal damage four weeks later in rats. PLoS One 8: e70513.

  24. HayrehSS, Zimmerman MB, Kimura A, Sanon A (2004) Central retinal arteryocclusion. Retinal survival time. Exp Eye Res 78: 723-736.

  25. HayrehSS, Weingeist TA (1980) Experimental occlusion of the central artery ofthe retina. IV: Retinal tolerance time to acute ischaemia. Br J Ophthalmol64: 818-825.

  26. HayrehSS, Kolder HE, Weingeist TA (1980) Central retinal artery occlusion andretinal tolerance time. Ophthalmology 87: 75-78.

  27. Murphy-LavoieH, Butler F, Hagan C (2012) Central retinal artery occlusion treated withoxygen: a literature review and treatment algorithm. Undersea Hyperb Med39:943-953

  28. HayrehSS, Weingeist TA (1980) Experimental occlusion of the central artery ofthe retina. I. Ophthalmoscopic and fluorescein fundus angiographicstudies. Br J Ophthalmol 64: 896-912.

  29. KawaguchiM, Furuya H, Patel PM (2005) Neuroprotective effects of anesthetic agents.J Anesth 19: 150-156.

  30. AlmaasR, Saugstad OD, Pleasure D, Rootwelt T (2000) Effect of barbiturates onhydroxyl radicals, lipid peroxidation, and hypoxic cell death in humanNT2-N neurons. Anesthesiology 92: 764-774.

  31. MillerKM, Wisnicki HJ, Buchman JP, Riley MJ, Repka MX, et al. (1988) The WilmerInformation System. A classification and retrieval system for informationon diagnosis and therapy in ophthalmology. Ophthalmology 95: 403-409.

  32. HayrehSS (1971) Pathogenesis of occlusion of the central retinal vessels. Am JOphthalmol 72: 998-1011.

  33. EagleR (2012) Eye Pathology: An Atlas and Text Lippincott Williams &Wilkins, Philadelphia, USA

  34. BeattyS, Au Eong KG (2000) Acute occlusion of the retinal arteries: currentconcepts and recent advances in diagnosis and management. J Accid EmergMed 17: 324-329.

  35. PlunkettO, Lip PL2, Lip GY1 (2014) Atrial fibrillation and retinal vein or arteryocclusion: looking beyond the eye. Br J Ophthalmol 98: 1141-1143.

  36. MangatHS1 (1995) Retinal artery occlusion. Surv Ophthalmol 40: 145-156.

  37. Joussen A, GardnerTW, KirchhofB, Ryan SJ (2007)Central Retinal Artery Occlusion in: Retinal Vascular Disease Springer,Berlin, Heidelberg

  38. FrançoisJ, Fryczkowski A (1978) The blood supply of the optic nerve. AdvOphthalmol 36: 164-173.

  39. AstrupJ, Siesjö BK, Symon L (1981) Thresholds in cerebral ischemia - theischemic penumbra. Stroke 12: 723-725.

  40. CourtneyM , Townsend Jr RDB, Evers MB, Mattox LK(2008) Sabiston Textbook ofSurgery: The Biological Basis of Modern Surgical Practice, (18th edn), PASaunders, Philadelphia

  41. ArnavielleS, Creuzot-Garcher C, Bron AM (2007) Anterior chamber paracentesis inpatients with acute elevation of intraocular pressure. Graefes Arch ClinExp Ophthalmol 245: 345-350.

  42. SimoneJN, Whitacre MM (1990) The effect of intraocular gas and fluid volumes onintraocular pressure. Ophthalmology 97: 238-243.

  43. AronowitzJD, Brubaker RF (1976) Effect of intraocular gas on intraocular pressure.Arch Ophthalmol 94: 1191-1196.

  44. LasseckJ, Jehle T, Feltgen N, Lagrèze WA (2008) Comparison of intraoculartonometry using three different non-invasive tonometers in children.Graefes Arch Clin Exp Ophtha lmol246: 1463-1466.

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